Skip to main content

Advertisement

Log in

Effect of different stages of Schistosoma mansoni infection on the parasite burden and immune response to Strongyloides venezuelensis in co-infected mice

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Multiple schistosome and soil-transmitted nematode infections are frequently reported in human populations living in tropical areas of developing countries. In addition to exposure factors, the host immune response plays an important role in helminth control and morbidity in hosts with multiple infections; however, these aspects are difficult to evaluate in human populations. In the current study, female Swiss mice were simultaneously co-infected with Strongyloides venezuelensis and Schistosoma mansoni or infected with St. venezuelensis at 2, 4, or 14 weeks after Sc. mansoni infection. The simultaneously infected mice showed a similar parasite burden for St. venezuelensis compared with mono-infected mice. In contrast, there was a significant reduction of St. venezuelensis burden (primarily during the migration of the larvae) in mice that were previously infected with Sc. mansoni at the acute or chronic phase. Independent of the stage of Sc. mansoni infection, the St. venezuelensis co-infection was capable of inducing IL-4 production in the small intestine, increasing the IgE concentration in the serum and increasing eosinophilia in the lungs and intestine. This result suggests that the nematode infection stimulates local type 2 immune responses independently of the schistosomiasis stage. Moreover, previous Sc. mansoni infection stimulated early granulocyte infiltration in the lungs and trematode-specific IgM and IgG1 production that recognized antigens from St. venezuelensis infective larvae; these immune responses would act in the early control of St. venezuelensis larvae. Our data suggest that the effect of multiple helminth infections on host susceptibility and morbidity largely depends on the species of parasite and the immune response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abruzzi A, Fried B (2011) Coinfection of Schistosoma (Trematoda) with bacteria, protozoa and helminthes. Adv Parasitol 77:1–85

    Article  PubMed  Google Scholar 

  • Belkaid Y, Blank RB, Suffia I (2006) Natural regulatory T cells and parasites: a common quest for host homeostasis. Immunol Rev 212:287–300

    Article  CAS  PubMed  Google Scholar 

  • Bonne-Année S, Hess JÁ, Abraham D (2011) Innate and adaptive immunity to the nematode Strongyloides stercoralis in a mouse model. Immunol Res 51:205–214

    Article  PubMed  Google Scholar 

  • Boros DL, Warren KS (1970) Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from Schistosoma mansoni eggs. J Exp Med 132:488–507

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bradley SL, Dines DE, Brewer NS (1978) Disseminated Strongyloides stercoralis in immunosuppressed host. Mayo Clin Proc 53:332–335

    CAS  PubMed  Google Scholar 

  • Brigandi RA, Rotman HL, Yutanawiboonchai W, Leon O, Nolan TJ, Schad GA, Abraham D (1996) Strongyloides stercoralis: role of antibody and complement in immunity to the third stage of larvae in BALB/cByJ mice. Exp Parasitol 82:279–289

    Article  CAS  PubMed  Google Scholar 

  • Burke ML, Jones MK, Gobert GN, Li YS, Ellis MK, McManus DP (2009) Immunopathogenesis of human schistosomiasis. Parasite Immunol 31:163–176

    Article  CAS  PubMed  Google Scholar 

  • Carvalho EM, Da Fonseca PA (2004) Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis. Parasite Immunol 26:487–497

    Article  CAS  PubMed  Google Scholar 

  • Concha AR, Harrington W Jr, Rogers AI (2005) Intestinal strongyloidiasis: recognition, management, and determinants of outcome. J Clin Gasteoenterol 39:203–211

    Article  Google Scholar 

  • Corrêa-Oliveira R, Golgher DB, Oliveira GC, Carvalho OS, Massara CL, Caldas IR, Colley DG, Gazzinelli G (2002) Infection with Schistosoma mansoni correlates with altered immune responses to Ascaris lumbricoides and hookworm. Acta Trop 83:123–132

    Article  PubMed  Google Scholar 

  • Curry AJ, Else KJ, Jones F, Bancroft A, Grencis RK, Dunne DW (1995) Evidence that cytokines-mediated immune interations induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris. J Exp Med 181:769–774

    Article  CAS  PubMed  Google Scholar 

  • De Jesus AR, Silva A, Santana LB, Magalhães A, de Jesus AA, de Almeida RP, Rêgo MA, Burattini MN, Pearce EJ, Carvalho EM (2002) Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni. J Infect Dis 185:98–105

    Article  PubMed  Google Scholar 

  • de Silva NR, Brooker S, Hotez PJ, Montresor A, Engles D, Saviole L (2003) Soil-transmitted helminth infection: updating the global picture. Trends Parasitol 19:547–551

    Article  PubMed  Google Scholar 

  • Dunne DW, Pearce EJ (1999) Immunology of hepatosplenic schistosomiasis mansoni: a human perspective. Microbes Infect 1:533–560

    Article  Google Scholar 

  • El-Malky M, Maruyama H, Hirabayashi Y, Shimada S, Yoshida A, Amano T, Tominaga A, Takatsu K, Ohta N (2003) Intraepithelial infiltration of eosinophils and their contribution to the elimination of adult intestinal nematode, Strongyloides venezuelensis in mice. Parasitol Int 52:71–79

    Article  PubMed  Google Scholar 

  • Fairfax BP, Makino S, Radhakrishnan J, Plant K, Leslie S, Dilthey A, Ellis P, Langford C, Vannberg FO, Knight JC (2012) Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat Genet 44:502–510

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fallon PG, Smith P, Dunne DW (1998) Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute Schistosoma mansoni infection. Eur J Immunol 28:1408–1416

    Article  CAS  PubMed  Google Scholar 

  • Fallon PG, Richardson EJ, McKenzie GJ, McKenzie AN (2000) Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J Immunol 164:2585–2591

    Article  CAS  PubMed  Google Scholar 

  • Fernandes A, Pereira ATM, Eechenazi PD, Schilter HC, Sousa ALS, Teixeira MM, Negrão-Corrêa D (2008) Evaluation of the immune response against Strongyloides venezuelensis in antigen-immunized or previously infected mice. Parasite Immunol 30:139–149

    Article  CAS  PubMed  Google Scholar 

  • Fleming FM, Brooker S, Geiger SM, Caldas IR, Corrêa-Oliveira R, Hotez PJ, Bethony JM (2006) Synergistic associations between hookworm and other helminth species in rural community in Brazil. Trop Med Int Health 11:56–64

    Article  PubMed  Google Scholar 

  • Gazzinelli SEP, Melo AL (2008) Interação entre Strongyloides venezuelensis e Schistosoma mansoni em camundongos da linhagem AKR/J. Rev Cienc Med Biol 7:149–155

    Google Scholar 

  • Genta RM (1989) Global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevention of disseminated disease. Rev Infect Dis 11:755–767

    Article  CAS  PubMed  Google Scholar 

  • Gryseels B, Polman K, Clerinx J, Kestens L (2006) Human schistosomiasis. Lancet 368:1106–1118

    Article  PubMed  Google Scholar 

  • Gryseels B (2012) Schistosomiasis. Infect Dis Clin North Am 26:383–397

    Article  PubMed  Google Scholar 

  • He YX, Salafsky B, Ramaswamy K (2005) Comparison of skin invasion among three major species of Schistosoma. Trends Parasitol 21:201–203

    Article  CAS  PubMed  Google Scholar 

  • Herbert DR, Lee JJ, Lee NA, Nolan TJ, Schad GA, Abraham D (2000) Role of IL-5 in innate and adaptive immunity to larval Strongyloides stercoralis in mice. J Immunol 165:4244–4551

    Article  Google Scholar 

  • Herbert DR, Orekov T, Perkins C, Finkelman FD (2008) IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J Immunol 181:7214–7220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hoffman KF, Cheever AW, Wynn TA (2000) IL-10 and the dangers of immune polarization: Excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol 164:6406–6416

    Article  Google Scholar 

  • Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections—the great neglected tropical diseases. J Clin Invest 118:1311–1321

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ivey CL, Williams FM, Collins PD, Jose PJ, Williams TJ (1995) Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit. Evidence for a role for C5a and interleukin-8. J Clin Invest 95:2986–2988

    Article  Google Scholar 

  • Krolewiecki AJ, Lammie P, Jacobson J, Gabrielli A-F, Levecke B, Socias E, Arias LM, Sosa N, Abraham D, Cimino R, Echazu A, Crudo F, Vercruysse J, Albonico M (2013) A public health response against Strongyloides stercoralis: time to look at soil-transmitted helminthiasis in full. PLoS Negl Trop Dis 7, e2165

    Article  PubMed Central  PubMed  Google Scholar 

  • Ligas JA, Kerepesi LA, Galioto AM, Lustigman NS, Nolan TJ, Schad GA, Abraham D (2003) Specificity and mechanism of immunoglobulin M (IgM)- and IgG-dependent protective immunity to larval Strongyloides stercoralis in mice. Infect Immun 71:6835–6843

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Loutfy MR, Wilson M, Keystone JS, Kain KC (2002) Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. Am J Trop Med Hyg 66:749–752

    PubMed  Google Scholar 

  • Maruyama H, Oosada Y, Yoshida A, Futakuchi M, Kawaguchi H, Zhang R, Gu J, Shirai S, Kojima S, Ohta N (2000) Protective mechanism against the intestinal nematode Strongyloides venezuelensis in Schistosoma japonicum-infected mice. Parasite Immunol 22:279–286

    Article  CAS  PubMed  Google Scholar 

  • Montes M, Sanchez C, Verdock K, Lake JE, Gonzalez E, Lopez G, Terashima A, Nolan T, Lewis DE, Gotuzzo E, White AC Jr (2009) Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. PLoS Negl Trop Dis 3, e456

    Article  PubMed Central  PubMed  Google Scholar 

  • Negrão-Corrêa D, Souza DG, Pinho V, Barsante MM, Souza AL, Teixeira MM (2004) Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice. Infect Immun 72:1135–1142

    Article  PubMed Central  PubMed  Google Scholar 

  • Negrão-Corrêa D, Pinho V, Souza DG, Pereira ANM, Fernandes A, Scheurmann K, Souza ALS, Teixeira MM (2006) Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the timely elimination of Strongyloides venezuelensis in mice, but not for intestinal IL-4 production. Int J Parasitol 36:1185–1195

    Article  PubMed  Google Scholar 

  • O’Connell AE, Hess JA, Santiago GA, Nolan TJ, Lok JB, Lee JJ, Abraham D (2011) Major basic protein from eosinophils and myeloperoxidase from neutrophils are required for protective immunity to Strongyloides stercoralis in mice. Infect Immun 79:2770–2778

    Article  PubMed Central  PubMed  Google Scholar 

  • Olsen A, van Lieshout L, Marti H, Polderman T, Polman K, Steinmann P, Stothard R, Thybo S, Verweij JJ, Magnussen P (2009) Strongyloidiasis—the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 103:967–972

    Article  PubMed  Google Scholar 

  • Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2:499–511

    Article  CAS  PubMed  Google Scholar 

  • Pearce EJ, Kane CM, Sun J, Taylor JJ, McKee AS, Cervil L (2004) Th2 response polarization during infection with helminth parasite Schistosoma mansoni. Immunol Rev 207:117–126

    Article  Google Scholar 

  • Pellegrino J, Macedo DG (1955) A simplified method for the concentration of cercariae. J Parasit 41:329–330

    Article  Google Scholar 

  • Porto ALF, Neva FA, Bittencourth H, Lisboa W, Thompson R, Alcântara L, Carvalho EM (2001) HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis. Parasite Immunol 23:503–507

    Article  CAS  PubMed  Google Scholar 

  • Porto MAF, Muniz A, Júnior JO, Carvalho EM (2002) Clinical and immunological consequences of the association between HTLV-1 and strongyloidiasis. Rev Soc Bras Med Trop 35:641–649

    Article  PubMed  Google Scholar 

  • Pullan R, Brooker S (2008) The health impact of polyparasitism in humans: are we under-estimating the burden of parasitic diseases? Parasitol 135:783–794

    Article  CAS  Google Scholar 

  • Pullan R, Bethony JM, Geiger SM, Cundill B, Correa-Oliveira R, Quinnell RJ, Brooker S (2008) Human helminth co-infection: analysis of spatial patterns and risk factors in a Brazilian community. PLoS Negl Trop Dis 2, e352

    Article  PubMed Central  PubMed  Google Scholar 

  • Pullan R, Bethony JM, Geiger SM, Correa-Oliveira R, Brooker S, Quinnell RJ (2010) Human helminth co-infection: no evidence of common genetic control of hookworm and Schistosoma mansoni infection intensity in a Brazilian community. Int J Parasitol 40:299–306

    Article  PubMed Central  PubMed  Google Scholar 

  • Rotman HL, Yutanawiboonchai W, Brigandi RA, Leon O, Gleich GJ, Nolan TJ, Schad GA, Abraham D (1996) Strongyloides stercoralis: eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice. Exp Parasitol 82:267–278

  • Sasaki Y, Yoshimoto T, Maruyama H, Tegoshi T, Ohta N, Arizono N, Nakanishi K (2005) IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell–dependent type 2 innate immunity. J Exp Med 202:607–616

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sato Y, Toma H (1990) Strongyloides venezuelensis infections in mice. Int J Parasitol 20:57–62

    Article  CAS  PubMed  Google Scholar 

  • Schär F, Trostdorf U, Giardina F, Khieu V, Muth S, Marti H, Vounatsou P, Odermatt P (2013) Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis 7, e2288

    Article  PubMed Central  PubMed  Google Scholar 

  • Siddiqui AA, Berk SL (2003) Strongyloidiasis. Curr Treatment Option 5:283–289

    Article  Google Scholar 

  • Silveira MR, Nunes KP, Cara DC, Souza DG, Corrêa A Jr, Teixeira MM, Negrão-Corrêa D (2002) Infection with Strongyloides venezuelensis induces transient airway eosinophilic inflammation, an increase in immunoglobulin E, and hyperresponsiveness in rats. Infect Immun 70:6263–6272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stadecker MJ, Hernandez HJ (1998) The immune response and immunopathology in infection with Schistosoma mansoni: a key role of major egg antigen Sm-p40. Parasite Immunol 20:217–221

    Article  CAS  PubMed  Google Scholar 

  • Stadecker ET, Asahi H, Finger E, Hernandez HJ, Rutitzky LI, Sun J (2004) The immunobiology of Th1 and high-pathology schistosomiasis. Immunol Rev 201:168–179

    Article  CAS  PubMed  Google Scholar 

  • Strath M, Warren DJ, Sanderson CJ (1985) Detection of eosinophils using an eosinophil peroxidase assay. Its use as an assay for eosinophil differentiation factors. J Immunol Meth 83:209–215

    Article  CAS  Google Scholar 

  • Tzanetou K, Tsiodra P, Delis V, Frangia K, Karakatsani E, Efstratopoulos A, Syriopoulou V (2005) Coinfection of Schistosoma mansoni and Strongyloides stercoralis in a patient with variceal bleeding. Infection 33:292–294

    Article  CAS  PubMed  Google Scholar 

  • WHO – World Health Organization (2014) Schistosomiasis. http://www.who.int/schistosomiasis/en/. Accessed 18 July 2014

  • Yoshida A, Maruyama H, Yabu Y, Amano T, Kobayakawa T, Ohta N (1999) Immune responses against protozoal and nematodal infection in mice with underlying Schistosoma mansoni infection. Parasitol Int 48:73–79

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil, Basic Parasitology Program). Acknowledgement is also due to José Carlos dos Reis and Selma Fernandes for their technical support of these experiments.

Conflict of interest

The authors declare that they have no competing interests.

Ethical standards

Experimental procedures received prior approval from the local animal ethics committee (protocol 097/07).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deborah Negrão-Corrêa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Rezende, M.C., Araújo, E.S., Moreira, J.M.P. et al. Effect of different stages of Schistosoma mansoni infection on the parasite burden and immune response to Strongyloides venezuelensis in co-infected mice. Parasitol Res 114, 4601–4616 (2015). https://doi.org/10.1007/s00436-015-4706-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4706-6

Keywords

Navigation