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Coinfection with Clonorchis sinensis modulates murine host response against Trichinella spiralis infection

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Abstract

Concomitant infections of different species of parasites are common in the field. Infection with one parasite species likely triggers host responses that may influence the subsequent infection of another species and alter disease outcomes. So far, the majority of studies have focused on single species parasite infection, and the mechanisms of protection induced by the first parasite infection against the secondary infection remain poorly defined. In this study, we assess the impact of trematode Clonorchis sinensis infection on the course of another tissue nematode Trichinella spiralis challenge. We observed that mice with preexisting C. sinensis infection had lower worm burden of intestinal T. spiralis than those infected with T. spiralis alone; mice with preexisting C. sinensis also had severe enteric histopathological changes and higher counts of intestinal Paneth cells in responses to T. spiralis challenge. The mRNA levels of interleukin (IL)-4, IL-10, IL-13, and tumor necrosis factor (TNF)-α from the small intestine and spleen of the different groups were analyzed using quantitative real-time polymerase chain reaction. Compared with that in mice infected with T. spiralis alone, the mRNA expression of IL-13 was significantly increased in the small intestine tissues and IL-4, IL-13, and TNF-α were significantly increased in the spleen tissues in the dually infected mice. Our findings suggest that a “preexisting” trematode infection of C. sinensis is a factor which contributes to reducing the establishment of T. spiralis adult worms in the small intestine.

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References

  • Abel Rahman EH, Abdel Megeed KN (2005) Cross-protection induced by cross-reactive antigen against Fasciola gigantica and Trichinella spiralis infections. J Egypt Soc Parasitol 35:281–294

    PubMed  Google Scholar 

  • Bazzone LE et al (2008) Coinfection with the intestinal nematode Heligmosomoides polygyrus markedly reduces hepatic egg-induced immunopathology and proinflammatory cytokines in mouse models of severe schistosomiasis. Infect Immun 76:5164–5172

    Article  PubMed  CAS  Google Scholar 

  • Behm CA, Ovington KS (2000) The role of eosinophils in parasitic helminth infections: insights from genetically modified mice. Parasitol Today 16:202–209

    Article  PubMed  CAS  Google Scholar 

  • Bian K, Zhong M, Harari Y, Lai M, Weisbrodt N, Murad F (2005) Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS-2 inhibition by Trichinella spiralis. Proc Natl Acad Sci USA 102:3936–3941

    Article  PubMed  CAS  Google Scholar 

  • Bokken GC et al (2012) Specific serum antibody responses following a Toxoplasma gondii and Trichinella spiralis co-infection in swine. Vet Parasitol 184:126–132

    Article  PubMed  CAS  Google Scholar 

  • Cox FE (2001) Concomitant infections, parasites and immune responses. Parasitology 122(Suppl):S23–S38

    Article  PubMed  Google Scholar 

  • de Sauvage FJ, Keshav S, Kuang WJ, Gillett N, Henzel W, Goeddel DV (1992) Precursor structure, expression, and tissue distribution of human guanylin. Proc Natl Acad Sci USA 89:9089–9093

    Article  PubMed  Google Scholar 

  • Donaldson LE, Schmitt E, Huntley JF, Newlands GF, Grencis RK (1996) A critical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth. Int Immunol 8:559–567

    Article  PubMed  CAS  Google Scholar 

  • Else KJ, Finkelman FD, Maliszewski CR, Grencis RK (1994) Cytokine-mediated regulation of chronic intestinal helminth infection. J Exp Med 179:347–351

    Article  PubMed  CAS  Google Scholar 

  • Furze RC, Hussell T, Selkirk ME (2006) Amelioration of influenza-induced pathology in mice by coinfection with Trichinella spiralis. Infect Immun 74:1924–1932

    Article  PubMed  CAS  Google Scholar 

  • Gebreselassie NG et al (2012) Eosinophils preserve parasitic nematode larvae by regulating local immunity. J Immunol 188:417–425

    Article  PubMed  CAS  Google Scholar 

  • Gessner A, Mohrs K, Mohrs M (2005) Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production. J Immunol 174:1063–1072

    PubMed  CAS  Google Scholar 

  • Herndon FJ, Kayes SG (1992) Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection. J Immunol 149:3642–3647

    PubMed  CAS  Google Scholar 

  • Huang S, Lu F, Chen Y, Huang B, Liu M (2013) Mast cell degranulation in human periodontitis. J Periodontol 84:248–255

    Article  PubMed  Google Scholar 

  • Ishikawa N, Wakelin D, Mahida YR (1997) Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected with Trichinella spiralis. Gastroenterology 113:542–549

    Article  PubMed  CAS  Google Scholar 

  • Jash A et al (2011) Topical application of porcine placenta extract inhibits the progression of experimental contact hypersensitivity. J Ethnopharmacol 133:654–662

    Article  PubMed  Google Scholar 

  • Jones LA et al (2010) IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. Eur J Immunol 40:426–436

    Article  PubMed  CAS  Google Scholar 

  • Kamal M, Wakelin D, Ouellette AJ, Smith A, Podolsky DK, Mahida YR (2001) Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T. spiralis-infected mice. Clin Exp Immunol 126:117–125

    Article  PubMed  CAS  Google Scholar 

  • Kamal M, Dehlawi MS, Brunet LR, Wakelin D (2002) Paneth and intermediate cell hyperplasia induced in mice by helminth infections. Parasitology 125:275–281

    Article  PubMed  CAS  Google Scholar 

  • Kazura JW, Aikawa M (1980) Host defense mechanisms against Trichinella spiralis infection in the mouse: eosinophil-mediated destruction of newborn larvae in vitro. J Immunol 124:355–361

    PubMed  CAS  Google Scholar 

  • Kim EM, Bae YM, Choi MH, Hong ST (2012) Cyst formation, increased anti-inflammatory cytokines and expression of chemokines support for Clonorchis sinensis infection in FVB mice. Parasitol Int 61:124–129

    Article  PubMed  CAS  Google Scholar 

  • Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky DK (1995) Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein. Gastroenterology 109:516–523

    Article  PubMed  CAS  Google Scholar 

  • Klion AD, Nutman TB (2004) The role of eosinophils in host defense against helminth parasites. J Allergy Clin Immunol 113:30–37

    Article  PubMed  CAS  Google Scholar 

  • Lai DH et al (2008) Molecular genetic profiles among individual Clonorchis sinensis adults collected from cats in two geographic regions of China revealed by RAPD and MGE-PCR methods. Acta Trop 107:213–216

    Article  PubMed  CAS  Google Scholar 

  • Lammas DA, Wakelin D, Mitchell LA, Tuohy M, Else KJ, Grencis RK (1992) Genetic influences upon eosinophilia and resistance in mice infected with Trichinella spiralis. Parasitology 105(Pt 1):117–124

    Article  PubMed  Google Scholar 

  • Lamont JT (1992) Mucus: the front line of intestinal mucosal defense. Ann N Y Acad Sci 664:190–201

    Article  PubMed  CAS  Google Scholar 

  • Lawrence CE, Paterson JC, Higgins LM, MacDonald TT, Kennedy MW, Garside P (1998) IL-4-regulated enteropathy in an intestinal nematode infection. Eur J Immunol 28:2672–2684

    Article  PubMed  CAS  Google Scholar 

  • Lee TD (1991) Helminthotoxic responses of intestinal eosinophils to Trichinella spiralis newborn larvae. Infect Immun 59:4405–4411

    PubMed  CAS  Google Scholar 

  • Maizels RM, Yazdanbakhsh M (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3:733–744

    Article  PubMed  CAS  Google Scholar 

  • McDermott JR, Humphreys NE, Forman SP, Donaldson DD, Grencis RK (2005) Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection. J Immunol 175:3207–3213

    PubMed  CAS  Google Scholar 

  • Michels CE et al (2009) Neither interleukin-4 receptor alpha expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis. Immunology 128(1 Suppl):e385–e394

    Article  PubMed  Google Scholar 

  • Muniz VS, Weller PF, Neves JS (2012) Eosinophil crystalloid granules: structure, function, and beyond. J Leukoc Biol 92:281–288

    Article  PubMed  CAS  Google Scholar 

  • Onah DN, Wakelin D (1999) Trypanosome-induced suppression of responses to Trichinella spiralis in vaccinated mice. Int J Parasitol 29:1017–1026

    Article  PubMed  CAS  Google Scholar 

  • Owen ILGMM, Pezzotti P, Pozio E (2005) Trichinella infection in a hunting population of Papua New Guinea suggests an ancient relationship between Trichinella and human beings. Trans R Soc Trop Med Hyg 99:618–624

    Article  PubMed  Google Scholar 

  • Paim RM et al (2012) Validation of reference genes for expression analysis in the salivary gland and the intestine of Rhodnius prolixus (Hemiptera, Reduviidae) under different experimental conditions by quantitative real-time PCR. BMC Res Notes 5:128

    Article  PubMed  CAS  Google Scholar 

  • Park MK et al (2011) Protease-activated receptor 2 is involved in Th2 responses against Trichinella spiralis infection. Korean J Parasitol 49:235–243

    Article  PubMed  CAS  Google Scholar 

  • Patel N, Kreider T, Urban JF Jr, Gause WC (2009) Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites. Int J Parasitol 39:13–21

    Article  PubMed  CAS  Google Scholar 

  • Pemberton AD et al (2004) Innate BALB/c enteric epithelial responses to Trichinella spiralis: inducible expression of a novel goblet cell lectin, intelectin-2, and its natural deletion in C57BL/10 mice. J Immunol 173:1894–1901

    PubMed  CAS  Google Scholar 

  • Podolsky DK et al (1993) Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. J Biol Chem 268:6694–6702

    PubMed  CAS  Google Scholar 

  • Poulsen SSNE, Olsen PS, Hess J, Kirkegaard P (1986) Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry 85:389–394

    Article  PubMed  CAS  Google Scholar 

  • Pozio E (2003) Foodborne and waterborne parasites. Acta Microbiol Pol 52(Suppl):83–96

    PubMed  Google Scholar 

  • Qian MBCY, Liang S, Yang GJ, Zhou XN (2012) The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma. Infect Dis Poverty 1:4

    Article  PubMed  Google Scholar 

  • Rousseau D, Le Fichoux Y, Stien X, Suffia I, Ferrua B, Kubar J (1997) Progression of visceral leishmaniasis due to Leishmania infantum in BALB/c mice is markedly slowed by prior infection with Trichinella spiralis. Infect Immun 65:4978–4983

    PubMed  CAS  Google Scholar 

  • Santaolalla R, Abreu MT (2012) Innate immunity in the small intestine. Curr Opin Gastroenterol 28:124–129

    Article  PubMed  CAS  Google Scholar 

  • Serna H, Porras M, Vergara P (2006) Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat. J Pharmacol Exp Ther 319:1104–1111

    Article  PubMed  CAS  Google Scholar 

  • Shang H, Wei H, Yue B, Xu P, Huang H (2009) Microsatellite analysis in two populations of Kunming mice. Lab Anim 43:34–40

    Article  PubMed  CAS  Google Scholar 

  • Shea-Donohue T, Urban JF Jr (2004) Gastrointestinal parasite and host interactions. Curr Opin Gastroenterol 20:3–9

    Article  PubMed  Google Scholar 

  • Specian RD, Oliver MG (1991) Functional biology of intestinal goblet cells. Am J Physiol 260:C183–C193

    PubMed  CAS  Google Scholar 

  • Suzuki T, Sasaki T, Takagi H, Sato K, Ueda K (2008) The effectors responsible for gastrointestinal nematode parasites, Trichinella spiralis, expulsion in rats. Parasitol Res 103:1289–1295

    Article  PubMed  Google Scholar 

  • Tan X, Hsueh W, Gonzalez-Crussi F (1993) Cellular localization of tumor necrosis factor (TNF)-alpha transcripts in normal bowel and in necrotizing enterocolitis. TNF gene expression by Paneth cells, intestinal eosinophils, and macrophages. Am J Pathol 142:1858–1865

    PubMed  CAS  Google Scholar 

  • Urban JF Jr, Noben-Trauth N, Schopf L, Madden KB, Finkelman FD (2001) Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites. J Immunol 167:6078–6081

    PubMed  CAS  Google Scholar 

  • Walsh R, Seth R, Behnke J, Potten CS, Mahida YR (2009) Epithelial stem cell-related alterations in Trichinella spiralis-infected small intestine. Cell Prolif 42:394–403

    Article  PubMed  CAS  Google Scholar 

  • Wang X et al (2009) Experimental model in rats for study on transmission dynamics and evaluation of Clonorchis sinensis infection immunologically, morphologically, and pathologically. Parasitol Res 106:15–21

    Article  PubMed  Google Scholar 

  • Wilson CL, Hepper KJ, Rudolph LA, Matrisian LM (1995) The metalloproteinase matrilysin is preferentially expressed by epithelial cells in a tissue-restricted pattern in the mouse. Mol Biol Cell 6:851–861

    PubMed  CAS  Google Scholar 

  • Wright KA (1979) Trichinella spiralis: an intracellular parasite in the intestinal phase. J Parasitol 65:441–445

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Endoh I, Hsu K, Tedla N, Endoh Y, Geczy CL (2011) S100A8 modulates mast cell function and suppresses eosinophil migration in acute asthma. Antioxid Redox Signal 14:1589–1600

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Xin-zhuan Su (LMVR/NIAID/NIH, USA) for his valuable advice and critical reading of the manuscript. This work was supported, in part, by grants from the National Basic Research Program of China (973 Program) (No. 2010CB530000) and the Natural Science Foundation of China to F. Lu (nos. 81071387 and 81271854).

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Correspondence to Shiguang Huang or Fangli Lu.

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Chen, Y., Huang, B., Huang, S. et al. Coinfection with Clonorchis sinensis modulates murine host response against Trichinella spiralis infection. Parasitol Res 112, 3167–3179 (2013). https://doi.org/10.1007/s00436-013-3493-1

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  • DOI: https://doi.org/10.1007/s00436-013-3493-1

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