Gonadectomy inhibits development of experimental amoebic liver abscess in hamsters through downregulation of the inflammatory immune response

Incidence of amoebic liver abscess (ALA) in human males is considerably higher than in females, suggesting a role for sex hormones in this parasite infection. We describe here the effect of hamster gonadectomization on the development of ALA. After monitoring the decrease of oestradiol in females and testosterone in males to undetectable levels by ELISA and Radio Immuno Assay (RIA) in serum, hamsters were intraportally infected with Entamoeba histolytica trophozoites and killed 7 days later. ALA was absent in 50% of male and 15% of female gonadectomized (Gdx) hamsters, in comparison with 100% infection in non‐Gdx controls. This protection against ALA in Gdx hamsters was concomitant to a comparatively scarce inflammatory infiltrate and necrosis surrounding clusters of trophozoites in the liver tissue, as well as to a lack of response of spleen cells to Con A, evaluated in proliferation assays. As tissue damage in ALA has been associated with a local inflammatory Th1 response, we determined the profile of response in hamsters by immunohistochemistry on liver sections. In contrast to strong Th1 responses in non‐Gdx animals, Gdx females and males exhibited Th2 and Th3 profiles of cytokines, respectively, suggesting that protection against ALA following gonadectomization, could be related to downregulation of liver Th1 response during amoebic infection.

[1]  J. Carrero,et al.  Late experimental amebic liver abscess in hamster is inhibited by cyclosporine and N-acetylcysteine. , 2007, Experimental and molecular pathology.

[2]  D. Kosec,et al.  Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. , 2007, The Journal of endocrinology.

[3]  C. D. Santos,et al.  Haematological and histopathological findings after ovariectomy in Trypanosoma cruzi infected mice. , 2007, Veterinary parasitology.

[4]  A. Scott,et al.  Involvement of Gonadal Steroids and Gamma Interferon in Sex Differences in Response to Blood-Stage Malaria Infection , 2006, Infection and Immunity.

[5]  V. Tsutsumi,et al.  Experimental amebiasis: a selected review of some in vivo models. , 2006, Archives of medical research.

[6]  E. Saavedra,et al.  Dehydroepiandrosterone decreases while cortisol increases in vitro growth and viability of Entamoeba histolytica. , 2006, Microbes and infection.

[7]  E. Tannich,et al.  Sexual Dimorphism in the Control of Amebic Liver Abscess in a Mouse Model of Disease , 2006, Infection and Immunity.

[8]  I. Marriott,et al.  Sexual dimorphism in innate immune responses to infectious organisms , 2006, Immunologic research.

[9]  E. Hoffman,et al.  Sexual dimorphism in immune response genes as a function of puberty , 2006, BMC Immunology.

[10]  C. Roberts,et al.  Parasite regulation by host hormones: an old mechanism of host exploitation? , 2005, Trends in parasitology.

[11]  M. Heineman,et al.  Sex hormones and the immune response in humans. , 2005, Human reproduction update.

[12]  P. Carmeliet,et al.  Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria , 2005, Infection and Immunity.

[13]  R. Straub,et al.  Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity , 2004, Lupus.

[14]  S. Klein,et al.  Hormonal and immunological mechanisms mediating sex differences in parasite infection , 2004, Parasite immunology.

[15]  J. Ibrahim,et al.  Effects of testosterone on blood leukocytes inPlasmodium berghei-infected mice , 2004, Parasitology Research.

[16]  A. Sapino,et al.  Estrogen Receptor (cid:1) Is a Novel Marker Expressed by Follicular Dendritic Cells in Lymph Nodes and Tumor-Associated Lymphoid Infiltrates , 2003 .

[17]  R. Jones,et al.  Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability. , 2003, The Journal of endocrinology.

[18]  S. Stanley Amoebiasis , 2003, The Lancet.

[19]  F. Wunderlich,et al.  B cells express intracellular but not surface receptors for testosterone and estradiol , 2002, Steroids.

[20]  Zhiyong Guo,et al.  Testosterone signaling in T cells and macrophages , 2002, Steroids.

[21]  C. Roberts,et al.  Sex-Associated Hormones and Immunity to Protozoan Parasites , 2001, Clinical Microbiology Reviews.

[22]  B. Spellberg,et al.  Type 1/Type 2 immunity in infectious diseases. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  S. Klein,et al.  The effects of hormones on sex differences in infection: from genes to behavior , 2000, Neuroscience & Biobehavioral Reviews.

[24]  V. Laudet,et al.  Hormones and nuclear receptors in schistosome development. , 2000, Parasitology today.

[25]  J. C. do Prado Jr.,et al.  Influence of male gonadal hormones on the parasitemia and humoral response of male Calomys callosus infected with the Y strain of Trypanosoma cruzi , 1999, Parasitology Research.

[26]  J. Cidlowski,et al.  Molecular control of immune/inflammatory responses: interactions between nuclear factor-kappa B and steroid receptor-signaling pathways. , 1999, Endocrine reviews.

[27]  D. Gaucher,et al.  Serum from Entamoeba histolytica-infected gerbils selectively suppresses T cell proliferation by inhibiting interleukin-2 production. , 1999, The Journal of infectious diseases.

[28]  J. Anselmo-Franci,et al.  Influence of female gonadal hormones on the parasitemia of female Calomys callosus infected with the “Y” strain of Trypanosoma cruzi , 1997, Parasitology Research.

[29]  F. Wunderlich,et al.  Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone. , 1997, The Journal of endocrinology.

[30]  K. Chadee,et al.  Interleukin (IL)-2, IL-4, and tumor necrosis factor-alpha responses during Entamoeba histolytica liver abscess development in gerbils. , 1997, The Journal of infectious diseases.

[31]  K. Sakabe,et al.  Sex hormones and the thymus in relation to thymocyte proliferation and maturation. , 1997, Archives of histology and cytology.

[32]  C. Roberts,et al.  Sex steroids, pregnancy-associated hormones and immunity to parasitic infection. , 1996, Parasitology today.

[33]  K. Chadee,et al.  Entamoeba histolytica modulates the nitric oxide synthase gene and nitric oxide production by macrophages for cytotoxicity against amoebae and tumour cells. , 1994, Immunology.

[34]  K. Chadee,et al.  Tumor necrosis factor alpha augments nitric oxide-dependent macrophage cytotoxicity against Entamoeba histolytica by enhanced expression of the nitric oxide synthase gene , 1994, Infection and immunity.

[35]  A. Prata,et al.  [Longitudinal radiologic study of the esophagus, in an endemic area of Chagas disease, in a period of 13 years]. , 1994, Revista da Sociedade Brasileira de Medicina Tropical.

[36]  F. Wunderlich,et al.  Testosterone impairs efficacy of protective vaccination against P. chabaudi malaria. , 1993, Vaccine.

[37]  A. Prata,et al.  Estudo radiológico longitudinal do esôfago, em área endêmica de doença de Chagas, em um período de seis anos , 1992 .

[38]  M. Denis,et al.  In vivo activation of macrophages by IFN‐γ to kill Entamoeba histolytica trophozoites in vitro , 1992 .

[39]  M. Denis,et al.  In vivo activation of macrophages by IFN-gamma to kill Entamoeba histolytica trophozoites in vitro. , 1992, Parasite immunology.

[40]  N. Christeff,et al.  Sex steroids, glucocorticoids, stress and autoimmunity , 1991, The Journal of Steroid Biochemistry and Molecular Biology.

[41]  F. Wunderlich,et al.  Testosterone and other gonadal factor(s) restrict the efficacy of genes controlling resistance to Plasmodium chabaudi malaria , 1991, Parasite immunology.

[42]  R. Hoff,et al.  A nine year prospective study of Chagas' disease in a defined rural population in northeast Brazil. , 1990, The American journal of tropical medicine and hygiene.

[43]  R. Kretschmer,et al.  Effector Mechanisms and Immunity to Amebas , 1990 .

[44]  M. Denis,et al.  Human Neutrophils Activated by Interferon‐γ and Tumour Necrosis Factor‐α Kill Entamoeba histolytica Trophozoites In Vitro , 1989 .

[45]  M. Denis,et al.  Human neutrophils activated by interferon-gamma and tumour necrosis factor-alpha kill Entamoeba histolytica trophozoites in vitro. , 1989, Journal of leukocyte biology.

[46]  C. Grossman Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. , 1989, Journal of steroid biochemistry.

[47]  B. Mock,et al.  Hormonal modulation of sex differences in resistance to Leishmania major systemic infections , 1988, Infection and immunity.

[48]  J. Ravdin,et al.  Review of the human immune mechanisms directed against Entamoeba histolytica. , 1986, Reviews of infectious diseases.

[49]  A. Martínez-Palomo,et al.  Cellular bases of experimental amebic liver abscess formation. , 1984, The American journal of pathology.

[50]  J. Dilawari,et al.  Progesterone-induced amoebic liver abscess in guinea-pigs--a new model. , 1983, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[51]  O. Jonasson,et al.  Amebic liver abscess. , 1982, Archives of surgery.

[52]  Gordon Hiroshi Sasaki,et al.  5A 1. Estrogen receptors—I 122. Prolactin, progesterone and actinomycin-D effects on specific estradiol binding in uterine tissues during pregnancy and lactation in vitro , 1974 .