Antiviral immune responses in the genital tract: clues for vaccines

Iwasaki, Akiko

doi:10.1038/nri2836

Cited by 150 publications

(156 citation statements)

References 132 publications

(123 reference statements)

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“…Animal studies have also demonstrated that TRMs mediate local protection against genital HSV‐2 infections (Shin, Kumamoto, Gopinath & Iwasaki, 2016). Therefore, induced immune cell protection against STIs in humans would likely require a potent resident memory T‐cell population (Iwasaki, 2010). Based on our findings, we speculate that despite vaccination, TRMs will not be equally induced and distributed throughout the FRT and will differ depending on women's age.…”

Section: Discussionmentioning

confidence: 99%

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

et al. 2018

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SummaryAs women age, susceptibility to systemic and genital infections increases. Tissue‐resident memory T cells (TRMs) are CD103+ CD8+ long‐lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+ CD8+ T cells were increased in postmenopausal compared to premenopausal women. Endometrial DCs from postmenopausal women were significantly more effective at inducing CD103 expression on allogeneic naïve CD8+ T cells than DCs from premenopausal women; CD103 upregulation was mediated through membrane‐bound TGFβ signaling. In contrast, cervical CD103+ T cells and DC numbers declined in postmenopausal women with age. Decreases in DCs correlated with decreased CD103+ T cells in endocervix, but not ectocervix. Our findings demonstrate a previously unrecognized compartmentalization of TRMs in the FRT of postmenopausal women, with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC induction capacity in the endometrium. These findings are relevant to understanding immune protection in the FRT and to the design of vaccines for women of all ages.

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Section: Discussionmentioning

confidence: 99%

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

et al. 2018

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“…This virus produces a lytic infection of epithelial cells in the skin and then spreads to nearby neurons, where it can persist for the life of the host (162). Local dendritic cells are also infected, at least early on (163)(164)(165)(166)(167).…”

Section: Srivastava and Ernst Recently Shed Light On How The Interactmentioning

confidence: 99%

“…Local dendritic cells are also infected, at least early on (163)(164)(165)(166)(167). T cells are thought to play a role in keeping the infection in a latent state in neurons, although this state can sporadically break down, resulting in viral replication and a skin lesion (162). CD8 ϩ T cells likely contribute to the control of infection by killing epithelial cells that become infected after the virus emerges from persistently infected neurons (162).…”

Section: Srivastava and Ernst Recently Shed Light On How The Interactmentioning

confidence: 99%

CD4⁺T Cells: Guardians of the Phagosome

Tubo

Jenkins

2014

Clin Microbiol Rev

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SUMMARY CD4 + T cells are key cells of the adaptive immune system that use T cell antigen receptors to recognize peptides that are generated in endosomes or phagosomes and displayed on the host cell surface bound to major histocompatibility complex molecules. These T cells participate in immune responses that protect hosts from microbes such as Mycobacterium tuberculosis , Cryptococcus neoformans , Leishmania major , and Salmonella enterica , which have evolved to live in the phagosomes of macrophages and dendritic cells. Here, we review studies indicating that CD4 + T cells control phagosomal infections asymptomatically in most individuals by secreting cytokines that activate the microbicidal activities of infected phagocytes but in a way that inhibits the pathogen but does not eliminate it. Indeed, we make the case that localized, controlled, persistent infection is necessary to maintain large numbers of CD4 + effector T cells in a state of activation needed to eradicate systemic and more pathogenic forms of the infection. Finally, we posit that current vaccines for phagosomal infections fail because they do not produce this “periodic reminder” form of CD4 + T cell-mediated immune control.

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“…As with other barrier surfaces, commensal microbiota, largely of the Lactobacillus species, shape the microenvironment of the vaginal tract. Lactobacilli produce hydrogen peroxide to prevent the outgrowth of harmful bacteria, and maintain the acidic pH of the vaginal mucosa through lactic acid production, which provides resistance against pathogens (9). Imbalances in the vaginal flora, called dysbiosis, result in outgrowth of pathogenic bacteria; however, the consequence of dysbiosis on genital antiviral immunity remains to be elucidated.…”

mentioning

confidence: 99%

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Kim

Chang

et al. 2016

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

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Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses, including type I IFN and proinflammatory cytokine production at infection sites, as well as induction of virusspecific CD4 and CD8 T-cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that IL-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of IFN-γ, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense.commensal microbiota | dysbiosis | IL-33 | herpes simplex virus type 2 | genital tract

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Antiviral immune responses in the genital tract: clues for vaccines

Cited by 150 publications

References 132 publications

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

CD4⁺T Cells: Guardians of the Phagosome

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

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Antiviral immune responses in the genital tract: clues for vaccines

Cited by 150 publications

References 132 publications

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

CD4+T Cells: Guardians of the Phagosome

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

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Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

Aging impacts CD103⁺CD8⁺ T cell presence and induction by dendritic cells in the genital tract

CD4⁺T Cells: Guardians of the Phagosome