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Gender and genetic control of resistance to intestinal amebiasis in inbred mice

Genes & Immunity volume 9, pages 452–461 (2008)Cite this article

Abstract

Resistance to the establishment of intestinal Entamoeba histolytica infection is dependent on the inbred mouse strain. In this work we used the inbred strains B6 (resistant), CBA (susceptible), B6CBAF1 and a backcross of B6CBAF1 to CBA to further examine the genetic basis of resistance. Mouse genotype was assessed with single nucleotide polymorphism and microsatellite markers and infection assessed by culture 9 days after intracecal E. histolytica challenge. The backcross population showed a male predisposition to culture positivity (P<0.002). F1 genotype at two loci on chromosomes 1 and 2 exhibited suggestive linkage with resistance to infection (P=0.0007 and 0.0200). Additional suggestive quantitative trait locus were observed on chromosomes 1, 9 and 13 for cecal parasite antigen load and histologic evidence of inflammation. Infection in C3H × B6 recombinant inbred mice supported the mapping data. Candidate B6 genes on chromosomes 1 and 2 were examined by microarray analysis of epithelial tissues from B6 vs CBA mice. This work shows a male predisposition to intestinal amebiasis and suggests that relatively few B6 loci can confer resistance in inbred mice. Future identification of regional candidate genes has implications for understanding the human variability to amebic infection.

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References

  1. Walsh JA . Problems in recognition and diagnosis of amebiasis: estimation of the global magnitude of morbidity and mortality. Rev Infect Dis 1986; 8: 228–238.

    Article  CAS  Google Scholar 

  2. Haque R, Duggal P, Ali IM, Hossain MB, Mondal D, Sack RB et al. Innate and acquired resistance to amebiasis in Bangladeshi children. J Infect Dis 2002; 186: 547–552.

    Article  CAS  Google Scholar 

  3. Haque R, Mondal D, Duggal P, Kabir M, Roy S, Farr BM et al. Entamoeba histolytica infection in children and protection from subsequent amebiasis. Infect Immun 2006; 74: 904–909.

    Article  CAS  Google Scholar 

  4. Irusen EM, Jackson TF, Simjee AE . Asymptomatic intestinal colonization by pathogenic Entamoeba histolytica in amebic liver abscess: prevalence, response to therapy, and pathogenic potential. Clin Infect Dis 1992; 14: 889–893.

    Article  CAS  Google Scholar 

  5. Blessmann J, Ali IK, Nu PA, Dinh BT, Viet TQ, Van AL et al. Longitudinal study of intestinal Entamoeba histolytica infections in asymptomatic adult carriers. J Clin Microbiol 2003; 41: 4745–4750.

    Article  Google Scholar 

  6. Gathiram V, Jackson TF . A longitudinal study of asymptomatic carriers of pathogenic zymodemes of Entamoeba histolytica. S Afr Med J 1987; 72: 669–672.

    CAS  PubMed  Google Scholar 

  7. Acuna-Soto R, Maguire JH, Wirth DF . Gender distribution in asymptomatic and invasive amebiasis. Am J Gastroenterol 2000; 95: 1277–1283.

    Article  CAS  Google Scholar 

  8. Houpt E, Barroso L, Lockhart L, Wright R, Cramer C, Lyerly D et al. Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin. Vaccine 2004; 22: 611–617.

    Article  CAS  Google Scholar 

  9. Haque R, Mondal D, Shu J, Roy S, Kabir M, Davis AN et al. Correlation of interferon-gamma production by peripheral blood mononuclear cells with childhood malnutrition and susceptibility to amebiasis. Am J Trop Med Hyg 2007; 76: 340–344.

    Article  CAS  Google Scholar 

  10. Houpt ER, Glembocki DJ, Obrig TG, Moskaluk CA, Lockhart LA, Wright RL et al. The mouse model of amebic colitis reveals mouse strain susceptibility to infection and exacerbation of disease by CD4+ T cells. J Immunol 2002; 169: 4496–4503.

    Article  CAS  Google Scholar 

  11. Asgharpour A, Gilchrist C, Baba D, Hamano S, Houpt E . Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells. Infect Immun 2005; 73: 4522–4529.

    Article  CAS  Google Scholar 

  12. Hamano S, Asgharpour A, Stroup SE, Wynn TA, Leiter EH, Houpt E . Resistance of C57BL/6 mice to amoebiasis is mediated by nonhemopoietic cells but requires hemopoietic IL-10 production. J Immunol 2006; 177: 1208–1213.

    Article  CAS  Google Scholar 

  13. Belley A, Keller K, Grove J, Chadee K . Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica: an in vitro model for colonic disease. Gastroenterology 1996; 111: 1484–1492.

    Article  CAS  Google Scholar 

  14. Petri Jr WA, Smith RD, Schlesinger PH, Murphy CF, Ravdin JI . Isolation of the galactose-binding lectin that mediates the in vitro adherence of Entamoeba histolytica. J Clin Invest 1987; 80: 1238–1244.

    Article  CAS  Google Scholar 

  15. Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 2002; 295: 1726–1729.

    Article  CAS  Google Scholar 

  16. Gottke MU, Keller K, Belley A, Garcia RM, Hollingsworth MA, Mack DR et al. Functional heterogeneity of colonic adenocarcinoma mucins for inhibition of Entamoeba histolytica adherence to target cells. J Eukaryot Microbiol 1998; 45: 17S–23S.

    Article  CAS  Google Scholar 

  17. Whitmore AC, Whitmore SP . Subline divergence within L.C. Strong's C3H and CBA inbred mouse strains. A review. Immunogenetics 1985; 21: 407–428.

    Article  CAS  Google Scholar 

  18. Miron M, Woody OZ, Marcil A, Murie C, Sladek R, Nadon R . A methodology for global validation of microarray experiments. BMC Bioinformatics 2006; 7: 333.

    Article  Google Scholar 

  19. Lotter H, Jacobs T, Gaworski I, Tannich E . Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease. Infect Immun 2006; 74: 118–124.

    Article  CAS  Google Scholar 

  20. Strachan NJ, Watson RO, Novik V, Hofreuter D, Ogden ID, Galan JE . Sexual dimorphism in campylobacteriosis. Epidemiol Infect (in press).

  21. Ge Z, Feng Y, Taylor NS, Ohtani M, Polz MF, Schauer DB et al. Colonization dynamics of altered Schaedler flora is influenced by gender, aging, and Helicobacter hepaticus infection in the intestines of Swiss Webster mice. Appl Environ Microbiol 2006; 72: 5100–5103.

    Article  CAS  Google Scholar 

  22. Fox JG, Wang TC, Rogers AB, Poutahidis T, Ge Z, Taylor N et al. Host and microbial constituents influence Helicobacter pylori-induced cancer in a murine model of hypergastrinemia. Gastroenterology 2003; 124: 1879–1890.

    Article  Google Scholar 

  23. Aebischer T, Laforsch S, Hurwitz R, Brombacher F, Meyer TF . Immunity against Helicobacter pylori: significance of interleukin-4 receptor alpha chain status and gender of infected mice. Infect Immun 2001; 69: 556–558.

    Article  CAS  Google Scholar 

  24. Kiyota M, Korenaga M, Nawa Y, Kotani M . Effect of androgen on the expression of the sex difference in susceptibility to infection with Strongyloides ratti in C57BL/6 mice. Aust J Exp Biol Med Sci 1984; 62 (Part 5): 607–618.

    Article  CAS  Google Scholar 

  25. Nagai Y, Akashi S, Nagafuku M, Ogata M, Iwakura Y, Akira S et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 2002; 3: 667–672.

    Article  CAS  Google Scholar 

  26. Wieland CW, Florquin S, Maris NA, Hoebe K, Beutler B, Takeda K et al. The MyD88-dependent, but not the MyD88-independent, pathway of TLR4 signaling is important in clearing nontypeable haemophilus influenzae from the mouse lung. J Immunol 2005; 175: 6042–6049.

    Article  CAS  Google Scholar 

  27. Clarke AR, Jones N, Pryde F, Adachi Y, Sansom OJ . 53BP1 deficiency in intestinal enterocytes does not alter the immediate response to ionizing radiation, but leads to increased nuclear area consistent with polyploidy. Oncogene 2007; 26: 6349–6355.

    Article  CAS  Google Scholar 

  28. Yan L, Stanley Jr SL . Blockade of caspases inhibits amebic liver abscess formation in a mouse model of disease. Infect Immun 2001; 69: 7911–7914.

    Article  CAS  Google Scholar 

  29. Cliffe LJ, Potten CS, Booth CE, Grencis RK . An increase in epithelial cell apoptosis is associated with chronic intestinal nematode infection. Infect Immun 2007; 75: 1556–1564.

    Article  CAS  Google Scholar 

  30. Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L . Isolation and characterization of human cervical-mucus glycoproteins. Biochem J 1983; 211: 13–22.

    Article  CAS  Google Scholar 

  31. Haley CS, Knott SA . A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 1992; 69: 315–324.

    Article  CAS  Google Scholar 

  32. Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by research grants from NIH (AI071373, AI052444), the Crohn's and Colitis Foundation of America, the Commonwealth of Virginia Technology Research Fund. SH was supported by a grant-in-Aid for Scientific Research from the Ministry of Education, Science, Technology, Sports and Culture of Japan and by the Mochida Memorial Foundation for Medical and Pharmaceutical Research. We thank Anna Velcich for provision of the Muc2 KO mice, Craig Coopersmith for the FVB mice, William A Petri Jr, for helpful advice and David Lyerly, Techlab, for the E. histolytica II ELISA kits. We acknowledge the UVA Research Histology Core of the Center for Research in Reproduction and thank Sharon Hoang of the UVA Digestive Health Center of Excellence Histology Core for immunohistochemistry support, whose work was partially supported by the Morphology/Imaging Core of the National Institutes of Health-funded Silvio O Conte Digestive Diseases Research Center (P30DK56703).

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Authors and Affiliations

  1. Department of Parasitology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    S Hamano

  2. Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, USA

    S Becker, A Asgharpour, Y P R Ocasio, S E Stroup & E Houpt

  3. Department of Microbiology, University of Virginia, Charlottesville, VA, USA

    M McDuffie

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  1. S Hamano
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  3. A Asgharpour
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  7. E Houpt
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Correspondence to E Houpt.

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The authors have no conflicting financial interests.

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Hamano, S., Becker, S., Asgharpour, A. et al. Gender and genetic control of resistance to intestinal amebiasis in inbred mice. Genes Immun 9, 452–461 (2008). https://doi.org/10.1038/gene.2008.37

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