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Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs.

Bień K, Sokołowska J, Bąska P, Nowak Z, Stankiewicz W, Krzyzowska M - Mediators Inflamm. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Lack of Fas or FasL leads to disturbances in antiviral immune response. Total counts of NK cells (a) NK/IFN-γ+ cells (b), CD4+ T cells (c), CD4+/IFN-γ+ T cells (d), CD8+ T cells (e), and CD8+/IFN-γ+ T cells (f) in cell suspensions prepared from the lungs isolated from Fas (−), FasL (−), and WT (C57BL/6) mice at 3, 7, 10, and 14 days of ECTV infection and from control, uninfected mice. The bars represent the mean from 5 separate experiments ± SEM.  *Significant differences with P ≤ 0.05 and **P ≤ 0.01 in comparison to Fas- and FasL-deficient mice.
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fig3: Lack of Fas or FasL leads to disturbances in antiviral immune response. Total counts of NK cells (a) NK/IFN-γ+ cells (b), CD4+ T cells (c), CD4+/IFN-γ+ T cells (d), CD8+ T cells (e), and CD8+/IFN-γ+ T cells (f) in cell suspensions prepared from the lungs isolated from Fas (−), FasL (−), and WT (C57BL/6) mice at 3, 7, 10, and 14 days of ECTV infection and from control, uninfected mice. The bars represent the mean from 5 separate experiments ± SEM.  *Significant differences with P ≤ 0.05 and **P ≤ 0.01 in comparison to Fas- and FasL-deficient mice.

Mentions: To determine the antiviral response, we measured total counts not only of NK1.1 (NK1.1+/CD3−) cells but also of CD4+ and CD8+ T cells in the lungs of C57BL/6, Fas (−), and FasL (−) mice at 3rd, 7th, 10th, and 14th d.p.i. (Figure 3). We found that lungs of wild-type mice showed significantly increased total counts of NK cells, CD4+, and CD8+ T cells at 3rd d.p.i in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figures 3(a), 3(c), and 3(e)). Furthermore, ECTV-infected wild-type mice showed significantly increased total counts of CD8+ T cells at 7th d.p.i. (P ≤ 0.05) (Figure 3(c)) and of CD4+ and CD8+ T cells at 14th d.p.i. (P ≤ 0.05) (Figures 3(c) and 3(e)). Given the role of IFN-γ in the early antiviral response, we next tested for the total counts of NK, CD4+, and CD8+ T cells expressing IFN-γ in the lungs (Figures 3(b), 3(d), and 3(f)). When comparing to ECTV-infected Fas- and FasL-deficient mice, wild-type mice showed significantly increased total counts of IFN-γ expressing NK cells at 3rd, 7th, and 10th d.p.i. (P ≤ 0.05) (Figure 3(b)). Furthermore, the lungs of wild-type mice revealed significantly increased total counts of CD4+ expressing IFN-γ during the whole infection period in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figure 3(d)). For the CD8+ T cells expressing IFN-γ, wild-type mice showed significantly higher total counts of these cells at 7th and 10th d.p.i. in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figure 3(f)).


Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs.

Bień K, Sokołowska J, Bąska P, Nowak Z, Stankiewicz W, Krzyzowska M - Mediators Inflamm. (2015)

Lack of Fas or FasL leads to disturbances in antiviral immune response. Total counts of NK cells (a) NK/IFN-γ+ cells (b), CD4+ T cells (c), CD4+/IFN-γ+ T cells (d), CD8+ T cells (e), and CD8+/IFN-γ+ T cells (f) in cell suspensions prepared from the lungs isolated from Fas (−), FasL (−), and WT (C57BL/6) mice at 3, 7, 10, and 14 days of ECTV infection and from control, uninfected mice. The bars represent the mean from 5 separate experiments ± SEM.  *Significant differences with P ≤ 0.05 and **P ≤ 0.01 in comparison to Fas- and FasL-deficient mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Lack of Fas or FasL leads to disturbances in antiviral immune response. Total counts of NK cells (a) NK/IFN-γ+ cells (b), CD4+ T cells (c), CD4+/IFN-γ+ T cells (d), CD8+ T cells (e), and CD8+/IFN-γ+ T cells (f) in cell suspensions prepared from the lungs isolated from Fas (−), FasL (−), and WT (C57BL/6) mice at 3, 7, 10, and 14 days of ECTV infection and from control, uninfected mice. The bars represent the mean from 5 separate experiments ± SEM.  *Significant differences with P ≤ 0.05 and **P ≤ 0.01 in comparison to Fas- and FasL-deficient mice.
Mentions: To determine the antiviral response, we measured total counts not only of NK1.1 (NK1.1+/CD3−) cells but also of CD4+ and CD8+ T cells in the lungs of C57BL/6, Fas (−), and FasL (−) mice at 3rd, 7th, 10th, and 14th d.p.i. (Figure 3). We found that lungs of wild-type mice showed significantly increased total counts of NK cells, CD4+, and CD8+ T cells at 3rd d.p.i in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figures 3(a), 3(c), and 3(e)). Furthermore, ECTV-infected wild-type mice showed significantly increased total counts of CD8+ T cells at 7th d.p.i. (P ≤ 0.05) (Figure 3(c)) and of CD4+ and CD8+ T cells at 14th d.p.i. (P ≤ 0.05) (Figures 3(c) and 3(e)). Given the role of IFN-γ in the early antiviral response, we next tested for the total counts of NK, CD4+, and CD8+ T cells expressing IFN-γ in the lungs (Figures 3(b), 3(d), and 3(f)). When comparing to ECTV-infected Fas- and FasL-deficient mice, wild-type mice showed significantly increased total counts of IFN-γ expressing NK cells at 3rd, 7th, and 10th d.p.i. (P ≤ 0.05) (Figure 3(b)). Furthermore, the lungs of wild-type mice revealed significantly increased total counts of CD4+ expressing IFN-γ during the whole infection period in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figure 3(d)). For the CD8+ T cells expressing IFN-γ, wild-type mice showed significantly higher total counts of these cells at 7th and 10th d.p.i. in comparison to Fas- and FasL-deficient mice (P ≤ 0.05) (Figure 3(f)).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus