Salt augments macrophage-driven host defense in the skin
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REPOSITORIES: ENA
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Project description:Immune cells regulate a hypertonic microenvironment in the skin; however, possible functions of increased skin Na+ concentrations are unknown. We found that Na+ accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania (L.) major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved L. major elimination. Finally, we found that increasing Na+ content in the skin by a high-salt diet boosted activation of macrophages in an Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.
2015-02-26 | E-MTAB-3343 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4350016 | biostudies-literature
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2015-11-11 | PXD003055 | Pride
Project description:Macrophage activation syndrome (MAS) is a life-threatening cytokine storm syndrome complicating systemic juvenile idiopathic arthritis (SJIA) and driven by IFN-gamma. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-gamma pathways as a pathologic link between SJIA-LD and MAS. Our objective was to mechanistically define the novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-gamma, IFN-induced chemokines, and alveolar macrophage expression of IFN-gamma-induced genes. Single-cell RNA-sequencing confirmed IFN-driven transcriptional changes across immune and parenchymal lung cell types. Resolution of MAS was associated with increased alveolar macrophage and interstitial lymphocytic infiltration. alveolar macrophage microarrays confirmed IFN-gamma-induced proinflammatory polarization during acute MAS, which switches towards an anti-inflammatory phenotype during MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and reset alveolar macrophagepolarization towards a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-gamma, both systemic feature of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-gamma-driven pulmonary inflammation replicating key features of SJIA-LD, and provides a model system for testing novel treatments directed towards SJIA-LD.
2021-09-12 | GSE169325 | GEO
Project description:IFN-gamma is essential for alveolar macrophage driven pulmonary inflammation in macrophage activation syndrome
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Project description:NF-κB1 (p50) impairs macrophage driven inflammatory response of the host against Helicobacter pylori infection
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Project description:Primary objectives: Characterization of the macrophage population subset that is modulated by enteric neurons
Primary endpoints: Characterization of the macrophage population subset that is modulated by enteric neurons via RNA sequencing
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Project description:Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a tissue-resident manner or can move between sites during infection is unclear. We show here that IL-25- or helminthic infection-induced inflammatory ILC2s are not tissue-resident but circulating cells, which arise from resting ILC2s residing in intestinal lamina propria and then migrate to mesenteric lymph nodes, spleen, lung, and liver. IL-25 induces rapid proliferation of the intestinal ILC2s and a change in their sensitivity to S1P-mediated chemotaxis, leading to lymphatic entry, blood circulation, and accumulation in periphery sites, including the lung where they contribute to anti-helminth defense and tissue repair. Our finding of cytokine-driven expansion and migration of innate lymphocytes, a behavioral parallel to the antigen-driven priming, expansion, and migration of adaptive lymphocytes to effector sites in distant tissues, provides a significant advance in our overall understanding of ILCs and indicates that ILCs complement adaptive immunity by providing both local and distant site effector protection during infection.
2018-01-08 | GSE104708 | GEO
Project description:NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.
2022-01-26 | GSE183577 | GEO