Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells

Roychoudhury, Pavitra; Swan, David A.; Duke, Elizabeth R; Corey, Lawrence; Zhu, Jia; Davé, Vrushank; Spuhler, Laura Richert; Lund, Jennifer M.; Prlic, Martin; Schiffer, Joshua T

doi:10.1172/jci132583

Cited by 48 publications

(31 citation statements)

References 69 publications

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“…cytokines upon infection. Modelling of the immune control and resolution of genital herpes lesions strongly suggests that CD8 + T cell stimulation is important for HSV control, probably with CD4 + T cell help [70,71], and these are likely to be primed by different DC subsets.…”

Section: Plos Pathogensmentioning

confidence: 99%

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

et al. 2021

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Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.

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Section: Plos Pathogensmentioning

confidence: 99%

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

et al. 2021

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“…Researches on human have revealed the similar developmental process and the persistence of pathogen-specific T RM in human skin. T RM specific for herpes simplex virus-2 accumulate in the genital skin and take part in eliminating the infected cells through the rapid production of cytokines at the time of recurrence 17 , 18 . Skin CD4 T cells reactive to varicella zoster virus persist with maintained function in elderly individuals 19 .…”

Section: Introductionmentioning

confidence: 99%

Skin T cells maintain their diversity and functionality in the elderly

et al. 2021

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Recent studies have highlighted that human resident memory T cells (TRM) are functionally distinct from circulating T cells. Thus, it can be postulated that skin T cells age differently from blood-circulating T cells. We assessed T-cell density, diversity, and function in individuals of various ages to study the immunologic effects of aging on human skin from two different countries. No decline in the density of T cells was noted with advancing age, and the frequency of epidermal CD49a+ CD8 TRM was increased in elderly individuals regardless of ethnicity. T-cell diversity and antipathogen responses were maintained in the skin of elderly individuals but declined in the blood. Our findings demonstrate that in elderly individuals, skin T cells maintain their density, diversity, and protective cytokine production despite the reduced T-cell diversity and function in blood. Skin resident T cells may represent a long-lived, highly protective reservoir of immunity in elderly people.

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“…β-Chemokines attract monocyte and T cell into the area of the lesion, IL-12 stimulates the secretion of CD4+ in a Th1 pattern which plays a role in activating cytotoxic T cells. Then, CD8+ cytotoxic T cells correspond started to clear the virus from the lesion [72,73] (Figure 4).…”

Section: The Immune Response Of the Human Body Against Hsv-1mentioning

confidence: 99%

An Updated Overview of Herpes Simplex Virus-1 Infection: Insights from Origin to Mitigation Measures

et al. 2021

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Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells

Abstract: Conflict of interest: LC is on the scientific advisory board for and holds stock in Immune Design Corp. and is a coinventor listed on several patents involving potential HSV vaccine development (US patents 6,

Cited by 48 publications

References 69 publications

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways

Skin T cells maintain their diversity and functionality in the elderly

An Updated Overview of Herpes Simplex Virus-1 Infection: Insights from Origin to Mitigation Measures

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