Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2 vaginal infection in mice

Krzyżowska, Małgorzata; Orłowski, Piotr; Bąska, Piotr; Bodera, Paweł; Zdanowski, Robert; Stankiewicz, Wanda

doi:10.1016/j.imbio.2014.07.021

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…We previously showed that mice lacking Fas or FasL expression show disturbances in regulation of Treg numbers during immune response [33, 34]. Here, we found increased total numbers of circulating Tregs in OVA-sensitized Fas- and FasL-deficient mice but no differences in the draining lymph nodes (Fig.…”

Section: Discussionsupporting

confidence: 57%

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

et al. 2017

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Objective and designThe aim of this study was to elucidate the role of apoptosis mediated through Fas/FasL pathway using the mouse model of atopic dermatitis (AD).Materials and treatment AD was induced by epicutaneous application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas−) and B6Smn.C3-Faslgld/J (FasL−) mouse strains.MethodsSkin samples were subjected to staining for Fas/FasL expression, M30 epitope and assessment of inflammatory response via immunohistochemical staining. Cytokine and chemokine production was assessed by real-time PCR.ResultsIn comparison to wild-type mice, OVA sensitization of Fas- and FasL-deficient mice led to increased epidermal and dermal thickness, collagen deposition and local inflammation consisting of macrophages, neutrophils and CD4+ T cells. Fas- and FasL-deficient mice showed increased total counts of regulatory T cells (Tregs) and IgE levels in blood as well as increased expression of IL-1β, IL-4, IL-5, IL-13 and TGF-1β mRNA in comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10, IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased.ConclusionsOur results show that lack of the Fas-induced apoptosis leads to exacerbation of AD characteristics such as Th2 inflammation and dermal thickening. Therefore, Fas receptor can play an important role in AD pathogenesis by controlling development of the local inflammation.

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Section: Discussionsupporting

confidence: 57%

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

et al. 2017

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“…Ligation of PD-L1 to its receptor PD-1 inhibits activation and expansion of CD8+ T cells, rendering them dysfunctional. Infection of DCs with live HSV-2 leads to an up-regulation of PD-L1 expression, as shown by Krzyzowska et al ( 52 ). Here, PD-L1 expression was conversely related with TA-AgNPs size, while an opposite effect was observed for TA-AuNPs.…”

Section: Discussionmentioning

confidence: 71%

Tannic Acid-Modified Silver and Gold Nanoparticles as Novel Stimulators of Dendritic Cells Activation

et al. 2018

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Silver nanoparticles (AgNPs) are promising new antimicrobial agents against a wide range of skin and mucosal pathogens. However, their interaction with the immune system is currently not fully understood. Dendritic cells (DCs) are crucial during development of T cell-specific responses against bacterial and viral pathogens. We have previously shown that tannic acid-modified silver nanoparticles (TA-AgNPs) consist of a promising microbicide against HSV-2. The aim of this study was to compare the ability of TA-AgNPs or TA-AuNPs of similar sizes (TA-Ag/AuNPs) to induce DCs maturation and activation in the presence of HSV-2 antigens when used at non-toxic doses. First, we used JAWS II DC line to test toxicity, ultrastructure as well as activation markers (MHC I and II, CD40, CD80, CD86, PD-L1) and cytokine production in the presence of TA-Ag/AuNPs. Preparations of HSV-2 treated with nanoparticles (TA-Ag/AuNPs-HSV-2) were further used to investigate HSV-2 antigen uptake, activation markers, TLR9 expression, and cytokine production. Additionally, we accessed proliferation and activation of HSV-2-specific T cells by DCs treated with TA-AgNP/AuNPs-HSV-2. We found that both TA-AgNPs and TA-AuNPs were efficiently internalized by DCs and induced activated ultrastructure. Although TA-AgNPs were more toxic than TA-AuNPs in corresponding sizes, they were also more potent stimulators of DCs maturation and TLR9 expression. TA-Ag/AuNPs-HSV-2 helped to overcome inhibition of DCs maturation by live or inactivated virus through up-regulation of MHC II and CD86 and down-regulation of CD80 expression. Down-regulation of CD40 expression in HSV-2-infected DCs was reversed when HSV-2 was treated with TA-NPs sized >30 nm. On the other hand, small-sized TA-AgNPs helped to better internalize HSV-2 antigens. HSV-2 treated with both types of NPs stimulated activation of JAWS II and memory CD8+ T cells, while TA-AgNPs treatment induced IFN-γ producing CD4+ and CD8+ T cells. Our study shows that TA-AgNPs or TA-AuNPs are good activators of DCs, albeit their final effect upon maturation and activation may be metal and size dependent. We conclude that TA-Ag/AuNPs consist of a novel class of nano-adjuvants, which can help to overcome virus-induced suppression of DCs activation.

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“…We have previously demonstrated that lack of Fas or FasL expression disturbs mounting of the antiviral response during vaginal HSV-2 infection due to decreased production of CXCL9 and IFN- γ and increased production of IL-10 and TGF- β 1 [ 39 , 40 ]. Here, we also observed disturbances in the pattern of cytokine and chemokine production in the lungs of Fas- and FasL-deficient mice during ECTV infection ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs

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Sokołowska

Bąska

et al. 2015

Mediators of Inflammation

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Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response.

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Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2 vaginal infection in mice

Cited by 6 publications

References 38 publications

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

Tannic Acid-Modified Silver and Gold Nanoparticles as Novel Stimulators of Dendritic Cells Activation

Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs

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