Volume 88, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Sex-based-differences are known to affect susceptibility to protozoan infections, but their effects on parasitemia and clinical symptoms in infections remain unclear. We examined the sex-based susceptibility of various mouse strains to Munich strain infection. In all strains, male mice exhibited significantly higher peak parasitemia and more severe anemia than female mice. Testosterone and estradiol-17β treatment caused an increase in parasitemia and aggravation of anemia. Orchidectomized male mice receiving testosterone exhibited smaller splenic macrophage populations three days after infection, smaller B cell populations 10 days after infection, and reduced splenic tumor necrosis factor-α and interferon-γ mRNA expression than mice that did not receive testosterone. Mice receiving estradiol-17β did not exhibit immunosuppressive effects. Thus, a weakened and delayed innate immunity response may lead to acquired immunity failure. The results suggested that testosterone directly affects T or B cells, leading to delayed acquired immunity, dramatically increased parasitemia, and severe anemia.


Article metrics loading...

Loading full text...

Full text loading...



  1. Bastos CV, Moreira SM, Passos LM, , 2004. Retrospective study (1998–2001) on canine babesiosis in Belo Horizonte, Minas Gerais, Brazil. Ann N Y Acad Sci 1026: 158160.[Crossref]
  2. Hornok S, Edelhofer R, Farkas R, , 2006. Seroprevalence of canine babesiosis in Hungary suggesting breed predisposition. Parasitol Res 99: 638642.[Crossref]
  3. Ikadai H, Tanaka H, Shibahara N, Matsuu A, Uechi M, Itoh N, Oshiro S, Kudo N, Igarashi I, Oyamada T, , 2004. Molecular evidence of infections with Babesia gibsoni parasites in Japan and evaluation of the diagnostic potential of a loop-mediated isothermal amplification method. J Clin Microbiol 42: 24652469.[Crossref]
  4. Máthé Á, Vörös K, Papp L, Reiczigel J, , 2006. Clinical manifestations of canine babesiosis in Hungary (63 cases). Acta Vet Hung 54: 367385.[Crossref]
  5. Krause PJ, , 2002. Babesiosis. Med Clin North Am 86: 361373.[Crossref]
  6. Feder HM, Jr Lawlor M, Krause PJ, , 2003. Babesiosis in pregnancy. N Engl J Med 349: 195196.[Crossref]
  7. Kamis AB, Ibrahim JB, , 1989. Effect of testosterone on blood leukocytes in Plasmodium berghei-infected mice. Parasitol Res 75: 611613.[Crossref]
  8. Cernetich A, Garver LS, Jedlicka AE, Klein PW, Kumar N, Scott AL, Klein SL, , 2006. Involvement of gonadal steroid and gamma interferon in sex differences in response to blood-stage malaria infection. Infect Immun 74: 31903203.[Crossref]
  9. Zhang Z, Chen L, Saito S, Kanagawa O, Sendo F, , 2000. Possible modulation by male sex hormone of Th1/Th2 function in protection against Plasmodium chabaudi chabaudi AS infection in mice. Exp Parasitol 96: 121129.[Crossref]
  10. Landgraf B, Kollaritsch H, Wiedermann G, Wernsdorfer WH, , 1994. Parasite density of Plasmodium falciparum malaria in Ghanaian schoolchildren: evidence for influence of sex hormones? Trans R Soc Trop Med Hyg 88: 7374.[Crossref]
  11. Alexander J, , 1988. Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major . Parasitology 96: 297302.[Crossref]
  12. do Prado JC, Jr Leal MP, Anselmo-Franci JA, de Andrade HF, Jr Kloetzel JK, , 1998. Influence of female gonadal hormones on the parasitemia of female Calomys callosus infected with the “Y” strain of Trypanosoma cruzi . Parasitol Res 84: 100105.[Crossref]
  13. do Prado JC, Jr Levy AM, Leal MP, Bernaed E, Kloetzel JK, , 1999. Influence of male gonadal hormones on the parasitemia and humoral response of male Calomys callosus infected with the Y strain of Trypanosoma cruzi . Parasitol Res 85: 826829.[Crossref]
  14. Daniels CW, Belosevic M, , 1995. Comparison of the course of infection with Giardia muris in male and female mice. Int J Parasitol 25: 131135.[Crossref]
  15. Daniels CW, Belosevic M, , 1994. Serum antibody responses by male and female C57Bl/6 mice infected with Giardia muris . Clin Exp Immunol 97: 424429.[Crossref]
  16. Benten WP, Wunderlich F, Mossmann H, , 1992. Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity. Exp Parasitol 75: 240247.[Crossref]
  17. Benten WP, Wunderlich F, Mossmann H, , 1992. Testosterone-induced suppression of self-healing Plasmodium chabaudi malaria: an effect not mediated by androgen receptors? J Endocrinol 135: 407413.[Crossref]
  18. Benten WP, Ulrich P, Kühn-Velten WN, Vohr HW, Wunderlich F, , 1997. Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone. J Endocrinol 153: 275281.[Crossref]
  19. Mock BA, Nancy CA, , 1988. Hormonal modulation of sex differences in resistance to Leishmania major systemic infections. Infect Immun 56: 33163319.
  20. Liesenfeld O, Nguyen TA, Pharke C, Suzuki Y, , 2001. Importance of gender and sex hormones in regulation of susceptibility of the small intestine to peroral infection with Toxoplasma gondii tissue cysts. J Parasitol 87: 14911493.[Crossref]
  21. Pung OJ, Luster MI, , 1986. Toxoplasma gondii: decreased resistance to infection in mice due to estrogen. Exp Parasitol 61: 4856.[Crossref]
  22. Roberts CW, Cruickshank SM, Alexander J, , 1995. Sex-determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production. Infect Immun 63: 25492555.
  23. Aguilar-Delfin I, Homer MJ, Wettstein PJ, Persing DH, , 2001. Innate resistance to Babesia infection is influenced by genetic background and gender. Infect Immun 69: 79557958.[Crossref]
  24. Clawson ML, Paciorkowski N, Rajan TV, La Vake C, Pope C, La Vale M, Wikel SK, Krause PJ, Radolf JD, , 2002. Cellular immunity, but not gamma interferon, is essential for resolution of Babesia microti infection in BALB/c mice. Infect Immun 70: 53045306.[Crossref]
  25. Eugui EM, Allison AC, , 1980. Differences in susceptibility of various mouse strains to haemoprotozoan infections: possible correlation with natural killer activity. Parasite Immunol 2: 277292.[Crossref]
  26. Habicht GS, Benach JL, Leichtling KD, Gocinski BL, Coleman JL, , 1983. The effect of age on the infection and immunoresponsiveness of mice to Babesia microti . Mech Ageing Dev 23: 357369.[Crossref]
  27. Hughes VL, Randolph SE, , 2001. Testosterone increases the transmission potential of tick-borne parasites. Parasitology 123: 365371.[Crossref]
  28. Ruebush MJ, Hanson WL, , 1979. Susceptibility of five strains of mice to Babesia microti of human origin. J Parasitol 65: 430433.[Crossref]
  29. Welc-Faleciak R, Bajer A, Bednarska M, Paziewska A, Siński E, , 2007. Long term monitoring of Babesia microti infection in BALB/c mice using nested PCR. Ann Agric Environ Med 14: 287290.
  30. Shikano S, Nakada K, Hashiguchi R, Shimada T, Ono K, , 1995. A short term in vitro cultivation of Babesia rodhaini and Babesia microti . J Vet Med Sci 57: 955957.[Crossref]
  31. Klein SL, , 2004. Hormonal and immunological mechanisms mediating sex differences in parasite infection. Parasite Immunol 26: 247264.[Crossref]
  32. Klein SL, Cernetich A, Hilmer S, Hoffman EP, Scott AL, Glass GE, , 2004. Differential expression of immunoregulatory genes in male and female Norway rats following infection with Seoul virus. J Med Virol 74: 180190.[Crossref]
  33. Pinzan CF, Ruas LP, Casabona-Fortunato AS, Carvalho FC, Roque-Barreira MC, , 2010. Immunological basis for the gender differences in murine Paracoccidioides brasiliensis infection. PLoS ONE 5: e10757.[Crossref]
  34. Roberts CW, Walker W, Alexander J, , 2001. Sex-associated hormones and immunity to protozoan parasites. Clin Microbiol Rev 14: 476488.[Crossref]
  35. Sheh A, Lee CW, Masumura K, Rickman BH, Nohmi T, Wogan GN, Fox JG, Schauer DB, , 2010. Mutagenic potency of Helicobacter pylori in the gastric mucosa of mice is determined by sex and duration of infection. Proc Natl Acad Sci USA 107: 1521715222.[Crossref]
  36. Textoris J, Ban LH, Capo C, Raoult D, Leone M, Mege JL, , 2010. Sex-related differences in gene expression following Coxiella burneti infection in mice: potential role of circadian rhythm. PLoS ONE 13: e12190.[Crossref]
  37. Schuurs SH, Verheul HA, , 1990. Effects of gender and sex steroids on the immune response. J Steroid Biochem 35: 157172.[Crossref]
  38. Marriott I, Huet-Hudson YM, , 2006. Sexual dimorphism in innate immune responses to infections organisms. Immunol Res 34: 177192.[Crossref]
  39. Spitzer JA, , 1999. Gender differences in some host defense mechanisms. Lupus 8: 380383.[Crossref]
  40. Walker W, Roberts CW, Ferguson DJ, Jebbari H, Alexander J, , 1997. Innate immunity to Toxoplasma gondii is influenced by gender and is associated with differences in interleukin-12 and gamma interferon production. Infect Immun 65: 11191121.
  41. Viselli SM, Stanziale S, Shults K, Kovacs WJ, Olsen NJ, , 1995. Castration alters peripheral immune function in normal male mice. Immunology 84: 337342.
  42. Mayr S, Walz CR, Angele P, Hernandez-Richter T, Chaudry IH, Loehe F, Jauch KW, Angele MK, , 2006. Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage. J Appl Physiol 101: 448453.[Crossref]
  43. Hannah MF, Bajic VB, Klein SL, , 2008. Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats. Brain Behav Immun 22: 503516.[Crossref]
  44. Leone M, Honstettre A, Lepidi H, Capo C, Bayard F, Raoult D, Mege JL, , 2004. Effect of sex on Coxiella burnetti infection: protective role of 17β-estradiol. J Infect Dis 189: 339345.[Crossref]
  45. Rivero JC, Inoue Y, Murakami NY, , 2002. Androgen- and estrogen-dependent sex differences in host resistance to Strongyloides venezuelensis infection in Wister rats. J Vet Med Sci 64: 457461.[Crossref]
  46. Ahmed SA, Talal N, , 1990. Sex hormones and the immune system – Part 2. Animal data. Baillieres Clin Rheumatol 4: 1331.[Crossref]
  47. Angele MK, Schwacha MG, Ayala A, Chaudry IH, , 2000. Effect of gender and sex hormones on immune responses following shock. Shock 14: 8190.[Crossref]
  48. Friedl R, Brunner M, Moeslinger T, Spieckermann PG, , 2000. Testosterone inhibits expression of inducible nitric oxide synthase in murine macrophages. Life Sci 68: 417429.[Crossref]
  49. Rettew JA, Huet-Hudson YM, Marriott I, , 2008. Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78: 432437.[Crossref]
  50. Kanda N, Tsuchida T, Tamaki K, , 1996. Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Clin Exp Immunol 106: 410415.[Crossref]
  51. Piliero SJ, Medici PT, Haber C, , 1968. The interrelationships of the endocrine and erythropoietic systems in the rat with special reference to mechanism of action of estradiol and testosterone. Ann N Y Acad Sci 149: 336355.[Crossref]

Data & Media loading...

  • Received : 25 May 2012
  • Accepted : 18 Oct 2012

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error