Sex Hormones and Modulation of Immunity against Leishmaniasis

Snider, Heidi; Lezama-Dávila, Claudio M.; Alexander, James; Satoskar, Abhay R.

doi:10.1159/000180265

Cited by 72 publications

(77 citation statements)

References 110 publications

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“…Indeed, gonadectomy and hormone therapy in mice suggest that estrogens are particularly associated with the ability of females but not males to produce IFNγ and a Th1 immune response (Roberts et al, 2001). Sex-differences in susceptibility to infection have also been observed for other parasites such as Plasmodium (Klein et al, 2008;Snider et al, 2009). We further found that protection against L. mexicana was gender-specific, with female hamsters being significantly protected by the DNA vaccine, while males failed to show protection.…”

supporting

confidence: 55%

“…Pregnancy (Osorio et al, 2008) and lactation (GomezOchoa et al, 2003) have both been found to reduce susceptibility to Leishmania infection in female hamsters. Gender differences in the incidence of visceral leishmaniasis has also been reported in human and dog populations, with males being usually more susceptible (Roberts et al, 2001;Snider et al, 2009). Sexual hormones are thought to contribute to the difference in cytokine production (Ahmadi & McCruden, 2006;Lezama-Davila et al, 2007;Roberts et al, 2001;Travi et al, 2002).…”

mentioning

confidence: 99%

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A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters againstLeishmania mexicana

et al. 2009

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Summary :Leishmaniasis is a group of diseases caused by protozoan parasites of the Leishmania genus. Previous studies have shown that a DNA vaccine encoding Leishmania donovani antigen nucleoside hydrolase 36 and L. mexicana glycoprotein 63 is protective in mice. We investigated here the efficacy of this DNA vaccine to induce protection in golden hamsters. Male hamsters were more susceptible to infection by Leishmania mexicana than females. Following immunization with two doses of the DNA vaccine, only females resulted protected while males developed normal lesions. Résumé

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supporting

confidence: 55%

mentioning

confidence: 99%

A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters againstLeishmania mexicana

et al. 2009

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“…However we do not consider this finding to be conclusive regarding the possible role of sex as demonstrated in the mouse model 33 . More studies will be done regarding the role of sex in susceptibility and/or resistance to the infection by L. (L.) mexicana in P. yucatanicus.…”

Section: This Is the First Study That Examines P Yucatanicus Clinicamentioning

confidence: 61%

Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania) mexicana

Sosa-Bibiano

Wynsberghe

Canto-Lara

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThere is not an experimental model of localized cutaneous leishmaniasis (LCL) caused by Leishmania (Leishmania) mexicana. The aim of the present study was to characterize the clinical and histological features of Peromyscus yucatanicus experimentally infected with L. (L.) mexicana. A total of 54 P. yucatanicus (groups of 18) were inoculated with 1x10 6 promastigotes of L. (L.) mexicana in the base of the tail. They were euthanized at three and six months post experimental infection. The control group was inoculated with RPMI-1640. The predominant clinical sign observed was a single ulcerated lesion in 27.77% (5/18) and in 11.11% (2/18) P. yucatanicus at three and six months respectively. The histological pattern described as chronic granulomatous inflammation with or without necrosis was found in 7/7 (100%) biopsies of euthanized P. yucatanicus at three (n = 5) and six (n = 2) months, respectively. These results resembled clinical and histological features caused by L. (L.) mexicana in humans, and support the possibility to employ P. yucatanicus as a novel experimental model to study LCL caused by this parasite.

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“…In particular, steroid hormones have been implicated as crucial contributors to the immune response either as enhancers, as is the situation with estrogens, or as endogenous inhibitors, as is the case with testosterone and glucocorticoids (22,23). This is best exemplified by the much higher incidence of autoimmune diseases such as multiple sclerosis in women, where the female to male ratio is significantly higher (2:1 to 3:1) (24,25).…”

mentioning

confidence: 99%

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

Fijak

Schneider

Klug

et al. 2011

The Journal of Immunology

182

154

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Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4+ T cells with a strong concomitant increase in the number of regulatory T cells (CD4+CD25+Foxp3+) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1–stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.

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Sex Hormones and Modulation of Immunity against Leishmaniasis

Cited by 72 publications

References 110 publications

A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters againstLeishmania mexicana

A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters againstLeishmania mexicana

Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania) mexicana

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

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