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Under the Influence: The Systemic Consequences of Helminth Infection

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Helminth Infections and their Impact on Global Public Health

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Abstract

It is well established that the survival and transmission of parasitic helminths (worms) in their mammalian hosts is dependent on down-regulation of the immune system; less well-characterised are the ramifications of helminth infection on other physiological functions. Immune modulation by helminth parasites has, for example, been linked to reduced susceptibility to inflammatory disorders, as well as poorer vaccine responses, and altered resistance to microbial pathogens. More broadly, systemic metabolism can also be affected, while in some instances the propensity for cancer is increased. In this chapter, I briefly review the pathways of immunomodulation and then consider the broader physiological and medical impact of helminths on the body.

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References

  • Allen JE, Maizels RM (2011) Diversity and dialogue in immunity to helminths. Nat Rev Immunol 11:375–388

    Article  CAS  PubMed  Google Scholar 

  • Araujo MI, Lopes AA, Medeiros M, Cruz AA, Sousa-Atta L, Solé D, Carvalho EM (2000) Inverse association between skin response to aeroallergen and Schistosoma mansoni infection. Int Arch Allergy Immunol 123:145–148

    Article  CAS  PubMed  Google Scholar 

  • Aravindhan V, Mohan V, Surendar J, Muralidhara Rao M, Pavankumar N, Deepa M, Rajagopalan R, Kumaraswami V, Nutman TB, Babu S (2010) Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83). PLoS Negl Trop Dis 4:e707

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Attallah AM, Abbas AT, Dessouky MI, El-emshaty HM, Elsheikha HM (2006) Susceptibility of neonate mice born to Schistosoma mansoni-infected and noninfected mothers to subsequent S. mansoni infection. Parasitol Res 99:137–145

    Article  CAS  PubMed  Google Scholar 

  • Babu S, Nutman TB (2012) Immunopathogenesis of lymphatic filarial disease. Semin Immunopathol 34:847–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bach JF (2018) The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat Rev Immunol 18:105–120

    Article  CAS  PubMed  Google Scholar 

  • Bager P, Arnved J, Rønborg S, Wohlfahrt J, Poulsen LK, Westergaard T, Petersen HW, Kristensen B, Thamsborg S, Roepstorff A, Kapel C, Melbye M (2010) Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. J Allergy Clin Immunol 125:123–130

    Article  PubMed  Google Scholar 

  • Blackwell AD, Tamayo MA, Beheim B, Trumble BC, Stieglitz J, Hooper PL, Martin M, Kaplan H, Gurven M (2015) Helminth infection, fecundity, and age of first pregnancy in women. Science 350:970–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Botelho MC, Alves H, Richter J (2016) Wound healing and cancer progression in Opisthorchis viverrini associated cholangiocarcinoma. Parasitol Res 115:2913–2914

    Article  PubMed  Google Scholar 

  • Bouchery T, Moyat M, Sotillo J, Silverstein S, Volpe B, Coakley G, Tsourouktsoglou TD, Becker L, Shah K, Kulagin M, Guiet R, Camberis M, Schmidt A, Seitz A, Giacomin P, Le Gros G, Papayannopoulos V, Loukas A, Harris NL (2020) Hookworms evade host immunity by secreting a deoxyribonuclease to degrade neutrophil extracellular traps. Cell Host Microbe 27(277–289):e6

    Google Scholar 

  • Brosschot TP, Reynolds LA (2018) The impact of a helminth-modified microbiome on host immunity. Mucosal Immunol 11:1039–1046

    Article  CAS  PubMed  Google Scholar 

  • Bullington BW, Klemperer K, Mages K, Chalem A, Mazigo HD, Changalucha J, Kapiga S, Wright PF, Yazdanbakhsh MM, Downs JA (2021) Effects of schistosomes on host anti-viral immune response and the acquisition, virulence, and prevention of viral infections: a systematic review. PLoS Pathog 17:e1009555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho L, Sun J, Kane C, Marshall F, Krawczyk C, Pearce EJ (2009) Mechanisms underlying helminth modulation of dendritic cell function. Immunology 126:28–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chawla A, Nguyen KD, Goh YP (2011) Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11:738–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chetty A, Darby MG, Vornewald PM, Martin-Alonso M, Filz A, Ritter M, McSorley HJ, Masson L, Smith K, Brombacher F, O'Shea MK, Cunningham AF, Ryffel B, Oudhoff MJ, Dewals BG, Layland LE, Horsnell WGC (2021) Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection. Cell Host Microbe 29(579–593):e5

    Google Scholar 

  • Coakley G, Harris NL (2020) The intestinal epithelium at the forefront of host-helminth interactions. Trends Parasitol 36(9):761–772. https://doi.org/10.1016/j.pt.2020.07.002

    Article  PubMed  Google Scholar 

  • Colebunders R, Njamnshi AK, Menon S, Newton CR, Hotterbeekx A, Preux PM, Hopkins A, Vaillant M, Siewe Fodjo JN (2021) Onchocerca volvulus and epilepsy: a comprehensive review using the Bradford Hill criteria for causation. PLoS Negl Trop Dis 15:e0008965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cooper PJ, Espinel I, Paredes W, Guderian RH, Nutman TB (1998) Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. J Infect Dis 178:1133–1138

    Article  CAS  PubMed  Google Scholar 

  • Cooper PJ, Chico ME, Losonsky G, Sandoval C, Espinel I, Sridhara R, Aguilar M, Guevara A, Guderian RH, Levine MM, Griffin GE, Nutman TB (2000) Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR. J Infect Dis 182:1199–1206

    Article  CAS  PubMed  Google Scholar 

  • Cooper PJ, Chico ME, Amorim LD, Sandoval C, Vaca M, Strina A, Campos AC, Rodrigues LC, Barreto ML, Strachan DP (2016) Effects of maternal geohelminth infections on allergy in early childhood. J Allergy Clin Immunol 137:899–906e2

    Article  PubMed  PubMed Central  Google Scholar 

  • Cooper PJ, Chico ME, Vaca MG, Sandoval CA, Loor S, Amorim LD, Rodrigues LC, Barreto ML, Strachan DP (2018) Effect of early-life geohelminth infections on the development of wheezing at 5 years of age. Am J Respir Crit Care Med 197:364–372

    Article  PubMed  PubMed Central  Google Scholar 

  • Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61:97–108

    Article  CAS  PubMed  Google Scholar 

  • Correale J, Farez MF (2011) The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol 233:6–11

    Article  CAS  PubMed  Google Scholar 

  • Correale J, Farez M, Razzitte G (2008) Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64:187–199

    Article  PubMed  Google Scholar 

  • Cortes A, Peachey L, Scotti R, Jenkins TP, Cantacessi C (2019) Helminth-microbiota cross-talk—a journey through the vertebrate digestive system. Mol Biochem Parasitol 233:111222

    Article  CAS  PubMed  Google Scholar 

  • Cortes-Selva D, Fairfax K (2021) Schistosome and intestinal helminth modulation of macrophage immunometabolism. Immunology 162:123–134

    Article  CAS  PubMed  Google Scholar 

  • Cortes-Selva D, Gibbs L, Maschek JA, Nascimento M, Van Ry T, Cox JE, Amiel E, Fairfax KC (2021) Metabolic reprogramming of the myeloid lineage by Schistosoma mansoni infection persists independently of antigen exposure. PLoS Pathog 17:e1009198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Croese J, Giacomin P, Navarro S, Clouston A, McCann L, Dougall A, Ferreira I, Susianto A, O'Rourke P, Howlett M, McCarthy J, Engwerda C, Jones D, Loukas A (2015) Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol 135:508–516

    Article  CAS  PubMed  Google Scholar 

  • Cruz AA, Cooper PJ, Figueiredo CA, Alcantara-Neves NM, Rodrigues LC, Barreto ML (2017) Global issues in allergy and immunology: parasitic infections and allergy. J Allergy Clin Immunol 140:1217–1228

    Article  PubMed  Google Scholar 

  • Dauby N, Goetghebuer T, Kollmann TR, Levy J, Marchant A (2012) Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis 12:330–340

    Article  PubMed  Google Scholar 

  • Desai P, Janova H, White JP, Reynoso GV, Hickman HD, Baldridge MT, Urban JF Jr, Stappenbeck TS, Thackray LB, Diamond MS (2021) Enteric helminth coinfection enhances host susceptibility to neurotropic flaviviruses via a tuft cell-IL-4 receptor signaling axis. Cell 184(1214–1231):e16

    Google Scholar 

  • Diemert DJ, Bottazzi ME, Plieskatt J, Hotez PJ, Bethony JM (2018) Lessons along the critical path: develo** vaccines against human helminths. Trends Parasitol 34:747–758

    Article  PubMed  Google Scholar 

  • Elias D, Akuffo H, Pawlowski A, Haile M, Schon T, Britton S (2005) Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent mycobacterium tuberculosis. Vaccine 23:1326–1334

    Article  CAS  PubMed  Google Scholar 

  • Elias D, Britton S, Aseffa A, Engers H, Akuffo H (2008) Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-β production. Vaccine 26:3897–3902

    Article  CAS  PubMed  Google Scholar 

  • El-Naccache DW, Hasko G, Gause WC (2020) Early events triggering the initiation of a type 2 immune response. Trends Immunol 42(2):151–164. https://doi.org/10.1016/j.it.2020.11.006

    Article  CAS  PubMed  Google Scholar 

  • Esen M, Mordmuller B, de Salazar PM, Adegnika AA, Agnandji ST, Schaumburg F, Hounkpatin AB, Bruckner S, Theisen M, Belard S, Ngoa UA, Issifou S, Yazdanbakhsh M, Kremsner PG (2012) Reduced antibody responses against plasmodium falciparum vaccine candidate antigens in the presence of Trichuris trichiura. Vaccine 30:7621–7624

    Article  CAS  PubMed  Google Scholar 

  • Evans H, Mitre E (2015) Worms as therapeutics for allergy and asthma: understanding why benefits in animal studies have not translated into clinical success. J Allergy Clin Immunol 135:343–353

    Article  PubMed  Google Scholar 

  • Ezenwa VO, Jolles AE (2015) Epidemiology. Opposite effects of anthelmintic treatment on microbial infection at individual versus population scales. Science 347:175–177

    Article  CAS  PubMed  Google Scholar 

  • Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR (2010) Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy 40:299–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feary J, Britton J, Leonardi-Bee J (2011) Atopy and current intestinal parasite infection: a systematic review and meta-analysis. Allergy 66:569–578

    Article  CAS  PubMed  Google Scholar 

  • Fleming JO, Weinstock JV (2015) Clinical trials of helminth therapy in autoimmune diseases: rationale and findings. Parasite Immunol 37:277–292

    Article  CAS  PubMed  Google Scholar 

  • Fried B, Reddy A, Mayer D (2011) Helminths in human carcinogenesis. Cancer Lett 305:239–249

    Article  CAS  PubMed  Google Scholar 

  • Furch BD, Koethe JR, Kayamba V, Heimburger DC, Kelly P (2020) Interactions of Schistosoma and HIV in sub-Saharan Africa: a systematic review. Am J Trop Med Hyg 102:711–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia HH (2018) Neurocysticercosis. Neurol Clin 36:851–864

    Article  PubMed  Google Scholar 

  • Garg SK, Croft AM, Bager P (2014) Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev 1:CD009400

    Google Scholar 

  • Giacomin P, Zakrzewski M, Croese J, Su X, Sotillo J, McCann L, Navarro S, Mitreva M, Krause L, Loukas A, Cantacessi C (2015) Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects. Sci Rep 5:13797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Graham AL (2008) Ecological rules governing helminth-microparasite coinfection. Proc Natl Acad Sci USA 105:566–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  PubMed  Google Scholar 

  • Guigas B, Molofsky AB (2015) A worm of one's own: how helminths modulate host adipose tissue function and metabolism. Trends Parasitol 31:435–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurven MD, Trumble BC, Stieglitz J, Blackwell AD, Michalik DE, Finch CE, Kaplan HS (2016) Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths? Evol Med Public Health 2016(1):338–357. https://doi.org/10.1093/emph/eow028

    Article  PubMed  PubMed Central  Google Scholar 

  • Harnett W, Harnett MM (2010) Helminth-derived immunomodulators: can understanding the worm produce the pill? Nat Rev Immunol 10:278–284

    Article  CAS  PubMed  Google Scholar 

  • Harris NL, Loke P (2017) Recent advances in Type-2-cell-mediated immunity: insights from helminth infection. Immunity 47:1024–1036

    Article  CAS  PubMed  Google Scholar 

  • Hayes KS, Bancroft AJ, Goldrick M, Portsmouth C, Roberts IS, Grencis RK (2010) Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris. Science 328:1391–1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hays R, Esterman A, Giacomin P, Loukas A, McDermott R (2015) Does Strongyloides stercoralis infection protect against type 2 diabetes in humans? Evidence from Australian aboriginal adults. Diabetes Res Clin Pract 107:355–361

    Article  PubMed  Google Scholar 

  • Helmby H (2015) Human helminth therapy to treat inflammatory disorders—where do we stand? BMC Immunol 16:12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hill IR, Denham DA, Scholtz CL (1985) Toxocara canis larvae in the brain of a British child. Trans R Soc Trop Med Hyg 79:351–354

    Article  CAS  PubMed  Google Scholar 

  • Hoerauf A, Buttner DW, Adjei O, Pearlman E (2003) Onchocerciasis. BMJ 326:207–210

    Article  PubMed  PubMed Central  Google Scholar 

  • Hussaarts L, van der Vlugt LE, Yazdanbakhsh M, Smits HH (2011) Regulatory B-cell induction by helminths: implications for allergic disease. J Allergy Clin Immunol 128:733–739

    Article  CAS  PubMed  Google Scholar 

  • Hussaarts L, Garcia-Tardon N, van Beek L, Heemskerk MM, Haeberlein S, van der Zon GC, Ozir-Fazalalikhan A, Berbee JF, Willems van Dijk K, van Harmelen V, Yazdanbakhsh M, Guigas B (2015) Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice. FASEB J 29:3027–3039

    Article  CAS  PubMed  Google Scholar 

  • Jardim-Botelho A, Raff S, Rodrigues Rde A, Hoffman HJ, Diemert DJ, Correa-Oliveira R, Bethony JM, Gazzinelli MF (2008) Hookworm, Ascaris lumbricoides infection and polyparasitism associated with poor cognitive performance in Brazilian schoolchildren. Tropical Med Int Health 13:994–1004

    Article  Google Scholar 

  • Kang SA, Choi JH, Baek KW, Lee DI, Jeong MJ, Yu HS (2021) Trichinella spiralis infection ameliorated diet-induced obesity model in mice. Int J Parasitol 51:63–71

    Article  CAS  PubMed  Google Scholar 

  • Keiser J, Utzinger J (2010) The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 73:197–230

    Article  PubMed  Google Scholar 

  • King CL, Malhotra I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW (1998) B cell sensitization to helminthic infection develops in utero in humans. J Immunol 160:3578–3584

    CAS  PubMed  Google Scholar 

  • Kolbekova P, Vetvicka D, Svoboda J, Skirnisson K, Leissova M, Syrucek M, Mareckova H, Kolarova L (2011) Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS. Parasitol Res 109:1267–1278

    Article  PubMed  Google Scholar 

  • Kroidl I, Saathoff E, Maganga L, Makunde WH, Hoerauf A, Geldmacher C, Clowes P, Maboko L, Hoelscher M (2016) Effect of Wuchereria bancrofti infection on HIV incidence in Southwest Tanzania: a prospective cohort study. Lancet 388:1912–1920

    Article  PubMed  Google Scholar 

  • Lacorcia M, Prazeres da Costa CU (2018) Maternal schistosomiasis: immunomodulatory effects with lasting impact on allergy and vaccine responses. Front Immunol 9:2960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SC, Tang MS, Lim YA, Choy SH, Kurtz ZD, Cox LM, Gundra UM, Cho I, Bonneau R, Blaser MJ, Chua KH, Loke P (2014) Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl Trop Dis 8:e2880

    Article  PubMed  PubMed Central  Google Scholar 

  • Lenzi JA, Sobral AC, Araripe JR, Grimaldi Filho G, Lenzi HL (1987) Congenital and nursing effects on the evolution of Schistosoma mansoni infection in mice. Mem Inst Oswaldo Cruz 82(Suppl 4):257–267

    Article  PubMed  Google Scholar 

  • Loffredo-Verde E, Bhattacharjee S, Malo A, Festag J, Kosinska AD, Ringelhan M, Rim Sarkar S, Steiger K, Heikenwaelder M, Protzer U, Prazeres da Costa CU (2020) Dynamic, helminth-induced immune modulation influences the outcome of acute and chronic hepatitis B virus infection. J Infect Dis 221:1448–1461

    Article  CAS  PubMed  Google Scholar 

  • Logan J, Navarro S, Loukas A, Giacomin P (2018) Helminth-induced regulatory T cells and suppression of allergic responses. Curr Opin Immunol 54:1–6

    Article  CAS  PubMed  Google Scholar 

  • Maizels RM (2020) Regulation of immunity and allergy by helminth parasites. Allergy 75:524–534

    Article  PubMed  Google Scholar 

  • Maizels RM, McSorley HJ (2016) Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 138:666–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maizels RM, McSorley HJ, Smyth DJ (2014) Helminths in the hygiene hypothesis—sooner or later? Clin Exp Immunol 177:38–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maizels RM, Smits HH, McSorley HJ (2018) Modulation of host immunity by helminths: the expanding repertoire of parasite effector molecules. Immunity 49:801–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malhotra I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW, King CL (1999) Helminth- and bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J Immunol 162:6843–6848

    CAS  PubMed  Google Scholar 

  • Malhotra I, McKibben M, Mungai P, McKibben E, Wang X, Sutherland LJ, Muchiri EM, King CH, King CL, LaBeaud AD (2015) Effect of antenatal parasitic infections on anti-vaccine IgG levels in children: a prospective birth cohort study in Kenya. PLoS Negl Trop Dis 9:e0003466

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maruszewska-Cheruiyot M, Donskow-Lysoniewska K, Doligalska M (2018) Helminth therapy: advances in the use of parasitic worms against inflammatory bowel diseases and its challenges. Helminthologia 55:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McFarlane AJ, McSorley HJ, Davidson DJ, Fitch PM, Errington C, Mackenzie KJ, Gollwitzer ES, Johnston CJ, MacDonald AS, Edwards MR, Harris NL, Marsland BJ, Maizels RM, Schwarze J (2017) Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota. J Allergy Clin Immunol 140(4):1068–1078.e6. https://doi.org/10.1016/j.jaci.2017.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McSorley HJ, Maizels RM (2012) Helminth infections and host immune regulation. Clin Microbiol Rev 25:585–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mishra PK, Palma M, Bleich D, Loke P, Gause WC (2014) Systemic impact of intestinal helminth infections. Mucosal Immunol 7:753–762

    Article  CAS  PubMed  Google Scholar 

  • Mostafa MH, Sheweita SA, O'Connor PJ (1999) Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 12:97–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Motran CC, Ambrosio LF, Volpini X, Celias DP, Cervi L (2017) Dendritic cells and parasites: from recognition and activation to immune response instruction. Semin Immunopathol 39:199–213

    Article  CAS  PubMed  Google Scholar 

  • Mpairwe H, Webb EL, Muhangi L, Ndibazza J, Akishule D, Nampijja M, Ngom-Wegi S, Tumusime J, Jones FM, Fitzsimmons C, Dunne DW, Muwanga M, Rodrigues LC, Elliott AM (2011) Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results. Pediatr Allergy Immunol 22(3):5–31

    Article  Google Scholar 

  • Mpairwe H, Tweyongyere R, Elliott A (2014) Pregnancy and helminth infections. Parasite Immunol 36:328–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murdoch ME (2010) Onchodermatitis. Curr Opin Infect Dis 23:124–131

    Article  PubMed  Google Scholar 

  • Mutapi F, Imai N, Nausch N, Bourke CD, Rujeni N, Mitchell KM, Midzi N, Woolhouse ME, Maizels RM, Mduluza T (2011) Schistosome infection intensity is inversely related to auto-reactive antibody levels. PLoS One 6:e19149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ndibazza J, Mpairwe H, Webb EL, Mawa PA, Nampijja M, Muhangi L, Kihembo M, Lule SA, Rutebarika D, Apule B, Akello F, Akurut H, Oduru G, Naniima P, Kizito D, Kizza M, Kizindo R, Tweyongere R, Alcock KJ, Muwanga M, Elliott AM (2012) Impact of anthelminthic treatment in pregnancy and childhood on immunisations, infections and eczema in childhood: a randomised controlled trial. PLoS One 7:e50325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ (2016) Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Robinson BA, Bundy DAP (1992) Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology 104:539–547

    Article  PubMed  Google Scholar 

  • Nono JK, Kamdem SD, Netongo PM, Dabee S, Schomaker M, Oumarou A, Brombacher F, Moyou-Somo R (2018) Schistosomiasis burden and its association with lower measles vaccine responses in school children from rural Cameroon. Front Immunol 9:2295

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Obieglo K, Feng X, Bollampalli VP, Dellacasa-Lindberg I, Classon C, Osterblad M, Helmby H, Hewitson JP, Maizels RM, Gigliotti Rothfuchs A, Nylen S (2016) Chronic gastrointestinal nematode infection mutes immune responses to mycobacterial infection distal to the gut. J Immunol 196:2262–2271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osbourn M, Soares DC, Vacca F, Cohen ES, Scott IC, Gregory WF, Smyth DJ, Toivakka M, Kemter AM, Le Bihan T, Wear M, Hoving D, Filbey KJ, Hewitson JP, Henderson H, Gonzàlez A, Errington C, Vermeren S, Astier A, Wallace WA, Schwarze J, Ivens AC, Maizels RM, McSorley HJ (2017) HpARI protein secreted by a helminth parasite suppresses interleukin-33. Immunity 47:739–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pabalan N, Singian E, Tabangay L, Jarjanazi H, Boivin MJ, Ezeamama AE (2018) Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: a systematic review and meta-analysis. PLoS Negl Trop Dis 12:e0005523

    Article  PubMed  PubMed Central  Google Scholar 

  • Rajamanickam A, Munisankar S, Bhootra Y, Dolla C, Thiruvengadam K, Nutman TB, Babu S (2019) Metabolic consequences of concomitant Strongyloides stercoralis infection in patients with type 2 diabetes mellitus. Clin Infect Dis 69:697–704

    Article  CAS  PubMed  Google Scholar 

  • Rajamanickam A, Munisankar S, Dolla C, Menon PA, Thiruvengadam K, Nutman TB, Babu S (2020a) Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis. PLoS Negl Trop Dis 14:e0008101

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rajamanickam A, Munisankar S, Thiruvengadam K, Menon PA, Dolla C, Nutman TB, Babu S (2020b) Impact of helminth infection on metabolic and immune homeostasis in non-diabetic obesity. Front Immunol 11:2195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramanan D, Bowcutt R, Lee SC, Tang MS, Kurtz ZD, Ding Y, Honda K, Gause WC, Blaser MJ, Bonneau RA, Lim YA, Loke P, Cadwell K (2016) Helminth infection promotes colonization resistance via type 2 immunity. Science 352:608–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rapin A, Harris NL (2018) Helminth-bacterial interactions: cause and consequence. Trends Immunol 39:724–733

    Article  CAS  PubMed  Google Scholar 

  • Red Eagle A, Chawla A (2010) In obesity and weight loss, all roads lead to the mighty macrophage. J Clin Invest 120:3437–3440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reese TA, Wakeman BS, Choi HS, Hufford MM, Huang SC, Zhang X, Buck MD, Jezewski A, Kambal A, Liu CY, Goel G, Murray PJ, Xavier RJ, Kaplan MH, Renne R, Speck SH, Artyomov MN, Pearce EJ, Virgin HW (2014) Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. Science 345:573–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reynolds LA, Smith KA, Filbey KJ, Harcus Y, Hewitson JP, Yebra M, Maizels RM (2014) Commensal-pathogen interactions in the intestinal tract: lactobacilli promote infection with, and are promoted by, helminth parasites. Gut Microbes 5:10–19

    Article  Google Scholar 

  • Reynolds LA, Finlay BB, Maizels RM (2015) Cohabitation in the intestine: interactions among helminth parasites, bacterial microbiota, and host immunity. J Immunol 195:4059–4066

    Article  CAS  PubMed  Google Scholar 

  • Reynolds LA, Redpath SA, Yurist-Doutsch S, Gill N, Brown EM, van der Heijden J, Brosschot TP, Han J, Marshall NC, Woodward SE, Valdez Y, Borchers CH, Perona-Wright G, Finlay BB (2017) Enteric helminths promote salmonella coinfection by altering the intestinal metabolome. J Infect Dis 215:1245–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riner DK, Ndombi EM, Carter JM, Omondi A, Kittur N, Kavere E, Korir HK, Flaherty B, Karanja D, Colley DG (2016) Schistosoma mansoni infection can jeopardize the duration of protective levels of antibody responses to immunizations against hepatitis B and tetanus toxoid. PLoS Negl Trop Dis 10:e0005180

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rojas A, Dvir E, Baneth G (2019) Insights on Spirocerca lupi, the carcinogenic dog nematode. Trends Parasitol 36(1):52–63. https://doi.org/10.1016/j.pt.2019.10.004

    Article  CAS  PubMed  Google Scholar 

  • Sabin EA, Araujo MI, Carvalho EM, Pearce EJ (1996) Impairment of tetanus toxoid-specific Th1-like immune responses in humans infected with Schistosoma mansoni. J Infect Dis 173:269–272

    Article  CAS  PubMed  Google Scholar 

  • Saenz SA, Taylor BC, Artis D (2008) Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev 226:172–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos P, Lorena VM, Fernandes Ede S, Sales IR, Nascimento WR, Gomes Yde M, Albuquerque MC, Costa VM, Souza VM (2016) Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection. Mem Inst Oswaldo Cruz 111:83–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scholte LLS, Pascoal-Xavier MA, Nahum LA (2018) Helminths and cancers from the evolutionary perspective. Front Med (Lausanne) 5:90

    Article  Google Scholar 

  • Schwartz C, Hams E, Fallon PG (2018) Helminth modulation of lung inflammation. Trends Parasitol 34:388–403

    Article  CAS  PubMed  Google Scholar 

  • Seydel LS, Petelski A, van Dam GJ, van der Kleij D, Kruize-Hoeksma YC, Luty AJ, Yazdanbakhsh M, Kremsner PG (2012) Association of in utero sensitization to Schistosoma haematobium with enhanced cord blood IgE and increased frequencies of CD5- B cells in African newborns. Am J Trop Med Hyg 86:613–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shea-Donohue T, Qin B, Smith A (2017) Parasites, nutrition, immune responses and biology of metabolic tissues. Parasite Immunol 39:5

    Article  Google Scholar 

  • Shen SW, Lu Y, Li F, Shen ZH, Xu M, Yao WF, Feng YB, Yun JT, Wang YP, Zhou L, Tong DX (2014) The potential long-term effect of previous schistosome infection may reduce the risk factors for cardiovascular diseases. Int J Cardiol 177:566–568

    Article  PubMed  Google Scholar 

  • Shen SW, Lu Y, Li F, Shen ZH, Xu M, Yao WF, Feng YB, Yun JT, Wang YP, Ling W, Qi HJ, Tong DX (2015) The potential long-term effect of previous schistosome infection reduces the risk of metabolic syndrome among Chinese men. Parasite Immunol 37:333–339

    Article  CAS  PubMed  Google Scholar 

  • Shepherd C, Navarro S, Wangchuk P, Wilson D, Daly NL, Loukas A (2015) Identifying the immunomodulatory components of helminths. Parasite Immunol 37:293–303

    Article  CAS  PubMed  Google Scholar 

  • Shimokawa C, Obi S, Shibata M, Olia A, Imai T, Suzue K, Hisaeda H (2019) Suppression of obesity by an intestinal helminth through interactions with intestinal microbiota. Infect Immun 87:6

    Article  Google Scholar 

  • Smallwood TB, Giacomin PR, Loukas A, Mulvenna JP, Clark RJ, Miles JJ (2017) Helminth immunomodulation in autoimmune disease. Front Immunol 8:453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573

    Article  CAS  PubMed  Google Scholar 

  • Smits HH, Hammad H, van Nimwegen M, Soullie T, Willart MA, Lievers E, Kadouch J, Kool M, Oosterhoud JK, Deelder AM, Lambrecht BN, Yazdanbakhsh M (2007) Protective effect of Schistosoma mansoni infection on allergic asthma depends on intensity and chronicity of infection. J Allergy Clin Immunol 120:932–940

    Article  CAS  PubMed  Google Scholar 

  • Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, Jones A, Brindley PJ, Loukas A (2009) A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells. PLoS Pathog 5:e1000611

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sobotkova K, Parker W, Leva J, Ruzkova J, Lukes J, Jirku PK (2019) Helminth therapy—from the parasite perspective. Trends Parasitol 35:501–515

    Article  PubMed  Google Scholar 

  • Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, Bethony JM, Loukas A (2012) The tumorigenic liver fluke Opisthorchis viverrini--multiple pathways to cancer. Trends Parasitol 28:395–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steel C, Guinea A, McCarthy JS, Ottesen EA (1994) Long-term effect of prenatal exposure to maternal microfilaraemia on immune responsiveness to filarial antigens. Lancet 343:890–893

    Article  CAS  PubMed  Google Scholar 

  • Straubinger K, Paul S, Prazeres da Costa O, Ritter M, Buch T, Busch DH, Layland LE, Prazeres da Costa CU (2014) Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation. J Allergy Clin Immunol 134(1271–1279):e10

    Google Scholar 

  • Strube C, Heuer L, Janacek E (2012) Toxocara infections in paratenic hosts. Vet Parasitol 193(4):375–389

    Article  PubMed  Google Scholar 

  • Su Z, Segura M, Stevenson MM (2006) Reduced protective efficacy of a blood-stage malaria vaccine by concurrent nematode infection. Infect Immun 74:2138–2144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su CW, Chen CY, Li Y, Long SR, Massey W, Kumar DV, Walker WA, Shi HN (2018) Helminth infection protects against high fat diet-induced obesity via induction of alternatively activated macrophages. Sci Rep 8:4607

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV (2003) Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 98:2034–2041

    Article  PubMed  Google Scholar 

  • Taylor MD, van der Werf N, Maizels RM (2012) T cells in helminth infection: the regulators and the regulated. Trends Immunol 33:181–189

    Article  CAS  PubMed  Google Scholar 

  • Taylor-Robinson DC, Maayan N, Soares-Weiser K, Donegan S, Garner P (2015) Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database Syst Rev 7:CD000371. https://doi.org/10.1002/14651858.CD000371.pub6:CD000371

    Article  Google Scholar 

  • Tweyongyere R, Nassanga BR, Muhwezi A, Odongo M, Lule SA, Nsubuga RN, Webb EL, Cose SC, Elliott AM (2019) Effect of Schistosoma mansoni infection and its treatment on antibody responses to measles catch-up immunisation in pre-school children: a randomised trial. PLoS Negl Trop Dis 13:e0007157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van den Biggelaar A, van Ree R, Roderigues LC, Lell B, Deelder AM, Kremsner PG, Yazdanbakhsh M (2000) Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356:1723–1727

    Article  PubMed  Google Scholar 

  • van den Biggelaar AH, Rodrigues LC, van Ree R, van der Zee JS, Hoeksma-Kruize YC, Souverijn JH, Missinou MA, Borrmann S, Kremsner PG, Yazdanbakhsh M (2004) Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J Infect Dis 189:892–900

    Article  PubMed  Google Scholar 

  • Varyani F, Fleming JO, Maizels RM (2017) Helminths in the gastrointestinal tract as modulators of immunity and pathology. Am J Physiol Gastrointest Liver Physiol 312:G537–G549

    Article  PubMed  PubMed Central  Google Scholar 

  • Voldsgaard A, Bager P, Garde E, Akeson P, Leffers AM, Madsen CG, Kapel C, Roepstorff A, Thamsborg SM, Melbye M, Siebner H, Sondergaard HB, Sellebjerg F, Sorensen PS (2015) Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect. Mult Scler 21:1723–1729

    Article  CAS  PubMed  Google Scholar 

  • Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M (2014) Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis 14:1150–1162

    Article  CAS  PubMed  Google Scholar 

  • Weinstock JV, Elliott DE (2013) Translatability of helminth therapy in inflammatory bowel diseases. Int J Parasitol 43:245–251

    Article  PubMed  Google Scholar 

  • Weinstock JV, Elliott DE (2014) Helminth infections decrease host susceptibility to immune-mediated diseases. J Immunol 193:3239–3247

    Article  CAS  PubMed  Google Scholar 

  • White MPJ, McManus CM, Maizels RM (2020) Regulatory T-cells in helminth infection: induction, function and therapeutic potential. Immunology 160:248–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson MS, Taylor MD, O'Gorman MT, Balic A, Barr TA, Filbey K, Anderton SM, Maizels RM (2010) Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol 40:1682–1696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiria AE, Djuardi Y, Supali T, Sartono E, Yazdanbakhsh M (2012) Helminth infection in populations undergoing epidemiological transition: a friend or foe? Semin Immunopathol 34:889–901

    Article  PubMed  Google Scholar 

  • Wiria AE, Sartono E, Supali T, Yazdanbakhsh M (2014) Helminth infections, type-2 immune response, and metabolic syndrome. PLoS Pathog 10:e1004140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wright VJ, Ame SM, Haji HS, Weir RE, Goodman D, Pritchard DI, Mohamed MR, Haji HJ, Tielsch JM, Stoltzfus RJ, Bickle QD (2009) Early exposure of infants to GI nematodes induces Th2 dominant immune responses which are unaffected by periodic anthelminthic treatment. PLoS Negl Trop Dis 3:e433

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wynn TA, Thompson RW, Cheever AW, Mentink-Kane MM (2004) Immunopathogenesis of schistosomiasis. Immunol Rev 201:156–167

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Grinchuk V, Smith A, Qin B, Bohl JA, Sun R, Notari L, Zhang Z, Sesaki H, Urban JF Jr, Shea-Donohue T, Zhao A (2013) Parasitic nematode-induced modulation of body weight and associated metabolic dysfunction in mouse models of obesity. Infect Immun 81:1905–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaiss MM, Harris NL (2016) Interactions between the intestinal microbiome and helminth parasites. Parasite Immunol 38:5–11

    Article  CAS  PubMed  Google Scholar 

  • Zaiss MM, Rapin A, Lebon L, Dubey LK, Mosconi I, Sarter K, Piersigilli A, Menin L, Walker AW, Rougemont J, Paerewijck O, Geldhof P, McCoy KD, Macpherson AJ, Croese J, Giacomin PR, Loukas A, Junt T, Marsland BJ, Harris NL (2015) The intestinal microbiota contributes to the ability of helminths to modulate allergic inflammation. Immunity 43:998–1010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK

    Rick M. Maizels

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  1. Department of Translational Research, N.T.M.S., Università di Pisa, Medical School, Pisa, Italy

    Fabrizio Bruschi

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Maizels, R.M. (2022). Under the Influence: The Systemic Consequences of Helminth Infection. In: Bruschi, F. (eds) Helminth Infections and their Impact on Global Public Health. Springer, Cham. https://doi.org/10.1007/978-3-031-00303-5_4

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