The Xs and Y of immune responses to viral vaccines

Klein, Sabra L.; Jedlicka, Anne; Pekosz, Andrew

doi:10.1016/s1473-3099(10)70049-9

Cited by 700 publications

(727 citation statements)

References 147 publications

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“…Our results add to an already sizeable literature demonstrating gender-based differences in innate and adaptive immune responses (24)(25)(26)(27)(28)(29); these differences influence the pathogenesis and outcomes of infectious and autoimmune diseases. Our study also provides one of the few analyses of testosterone and HCV infection.…”

Section: Discussionsupporting

confidence: 67%

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Wang

Zhang

Yang

2017

Experimental and Therapeutic Medicine

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Abstract. It has previously been suggested that men and women demonstrate differing immune responses to hepatitis C virus (HCV) infection, resulting in the investigation of the role of sex hormones and if they influence the anti-HCV response. The present study aimed to examine if hormone levels were associated with interferon (IFN) signaling pathways in peripheral blood mononuclear cells of 131 patients infected with HCV and 113 healthy controls. HCV infection was diagnosed based on the presence of anti-HCV antibodies and HCV RNA in serum. Expression of testosterone and estrogen was measured at the protein level using a competitive chemiluminescence immunoassay, and at the mRNA level using reverse transcription-quantitative polymerase chain reaction. HCV-infected males had increased levels of estrogen and a decreased ratio of testosterone to estrogen compared with healthy male controls (all P<0.001). HCV-infected patients demonstrated a significantly decreased expression of IFN and retinoic acid-induced gene protein I (RIG-I), RIG-I mRNA compared with controls. Pearson correlation analysis revealed that among males, levels of RIG-I correlated with levels of IFN-β mRNA (r=0.460), testosterone (r=-0.500), and the ratio of testosterone to estrogen (r=-0.477; all P<0.001). However, levels of RIG-I did not correlate with levels of IFN-α mRNA (r=0.158) or estrogen (r=0.173; both P>0.05). These results suggested that testosterone or the ratio of testosterone to estrogen may inhibit RIG-I signaling and thereby influence immune responses to HCV infection. IntroductionHepatitis C virus (HCV), a single-strand RNA virus of the Flaviviridae family, infects approximately 170 million people worldwide (1). HCV replication in infected individuals triggers an innate immune response that is often ineffective: As many as 80% of HCV-infected patients cannot eliminate the virus and develop chronic hepatitis, cirrhosis, and even liver cancer (2). Innate immune responses to HCV infection differ between men and women (3-5), leading to the question of whether sex hormones may influence these responses.Innate immune responses are induced when pattern recognition receptors (PRRs), which are expressed on immune cells, especially antigen-presenting cells, recognize viral genetic material (6). PRRs include Rig-like helicase receptors, NOD-nucleotide binding oligomerization domain-like receptors and Toll-like receptors. PRRs trigger signaling pathways that induce the production and release of cytokines such as the type I interferons IFN-α and IFN-βThe central PRR activated in response to RNA virus infection is retinoic acid-induced gene protein I (RIG-I), a 5'-triphosphorylated, uncapped RNA-binding DexD/H-box helicase (7). After binding to viral RNA, RIG-I induces a host response in which the amino-caspase activation and recruitment domains (CARDs) interact with the amino-terminal CARD of the IFN-β promoter-stimulator 1 (IPS-1) (7).The present study explored whether differences in sex hormone levels between men and women may lead to differenc...

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Section: Discussionsupporting

confidence: 67%

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Wang

Zhang

Yang

2017

Experimental and Therapeutic Medicine

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“…By definition, this variable was 0 in all persons attending the first-and second-measurement wave and took the value 1 in 32 out of 137 persons attending the last-measurement wave, while remaining 0 in the other 105 persons attending this wave. Moreover, gender and its interaction term with time postvaccination were included in the initially entered set of explanatory variables because of sex differences in immune antibody responses to vaccines described in the literature (16,17).…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population

Huijskens

Rossen

Mulder

et al. 2011

Clin. Vaccine Immunol.

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“…Women almost universally respond as well or better than men to antibody-inducing vaccinations (1). For example, healthy women treated with the trivalent inactivated influenza vaccine generate a greater antibody titer than men (2).…”

mentioning

confidence: 99%

Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation

Kissick

Sanda

Dunn

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

257

190

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The hormonal milieu influences immune tolerance and the immune response against viruses and cancer, but the direct effect of androgens on cellular immunity remains largely uncharacterized. We therefore sought to evaluate the effect of androgens on murine and human T cells in vivo and in vitro. We found that murine androgen deprivation in vivo elicited RNA expression patterns conducive to IFN signaling and T-cell differentiation. Interrogation of mechanism showed that testosterone regulates T-helper 1 (Th1) differentiation by inhibiting IL-12-induced Stat4 phosphorylation: in murine models, we determined that androgen receptor binds a conserved region within the phosphatase, Ptpn1, and consequent up-regulation of Ptpn1 then inhibits IL-12 signaling in CD4 T cells. The clinical relevance of this mechanism, whereby the androgen milieu modulates CD4 T-cell differentiation, was ascertained as we found that androgen deprivation reduced expression of Ptpn1 in CD4 cells from patients undergoing androgen deprivation therapy for prostate cancer. Our findings, which demonstrate a clinically relevant mechanism by which androgens inhibit Th1 differentiation of CD4 T cells, provide rationale for targeting androgens to enhance CD4-mediated immune responses in cancer or, conversely, for modulating androgens to mitigate CD4 responses in disorders of autoimmunity.immunomodulation | cancer immunotherapy | prostate neoplasm

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The Xs and Y of immune responses to viral vaccines

Cited by 700 publications

References 147 publications

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population

Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation

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