IFN-γ production by innate immune cells is sufficient for development of hypersensitivity pneumonitis

2005 ◽  
Vol 35 (6) ◽  
pp. 1928-1938 ◽  
Author(s):  
Stephanie Nance ◽  
Richard Cross ◽  
Ae-Kyung Yi ◽  
Elizabeth A. Fitzpatrick
Keyword(s):  
Immune Cells ◽  
Hypersensitivity Pneumonitis ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Ifn Γ

scholarly journals BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection

2017 ◽  
Vol 214 (5) ◽  
pp. 1313-1331 ◽  
Author(s):  
Shoko Kitada ◽  
Hisako Kayama ◽  
Daisuke Okuzaki ◽  
Ritsuko Koga ◽  
Masao Kobayashi ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Parasite Burden ◽  
Innate Immune ◽  
Negative Regulator ◽  
Innate Immune Cells ◽  
Th17 Response ◽  
Ifn Γ ◽  
Cruzi Infection

Inappropriate IL-17 responses are implicated in chronic tissue inflammation. IL-23 contributes to Trypanosoma cruzi–specific IL-17 production, but the molecular mechanisms underlying regulation of the IL-23–IL-17 axis during T. cruzi infection are poorly understood. Here, we demonstrate a novel function of BATF2 as a negative regulator of Il23a in innate immune cells. IL-17, but not IFN-γ, was more highly produced by CD4+ T cells from spleens and livers of T. cruzi–infected Batf2−/− mice than by those of wild-type mice. In this context, Batf2−/− mice showed severe multiorgan pathology despite reduced parasite burden. T. cruzi–induced IL-23 production was increased in Batf2−/− innate immune cells. The T. cruzi–induced enhanced Th17 response was abrogated in Batf2−/−Il23a−/− mice. The interaction of BATF2 with c-JUN prevented c-JUN–ATF-2 complex formation, inhibiting Il23a expression. These results demonstrate that IFN-γ–inducible BATF2 in innate immune cells controls Th17-mediated immunopathology by suppressing IL-23 production during T. cruzi infection.

scholarly journals The Life Cycle Stages of Pneumocystis murina Have Opposing Effects on the Immune Response to This Opportunistic Fungal Pathogen

2016 ◽  
Vol 84 (11) ◽  
pp. 3195-3205 ◽  
Author(s):  
Heather M. Evans ◽  
Grady L. Bryant ◽  
Beth A. Garvy
Keyword(s):  
Cell Wall ◽  
Life Cycle ◽  
Immune Responses ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Content Type ◽  
Life Cycle Stages ◽  
Ifn Γ

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina . The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4 + T cells that produce IFN-γ. In vitro , bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4 + T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro , suggesting that the trophic forms dampen cyst-induced inflammation in vivo .

scholarly journals Differential Regulation of Macrophage Interleukin-1 (IL-1), IL-12, and CD80-CD86 by Two Bacterial Toxins

1999 ◽  
Vol 67 (10) ◽  
pp. 5275-5281 ◽  
Author(s):  
Dennis L. Foss ◽  
Michael J. Zilliox ◽  
Michael P. Murtaugh
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Interleukin 1 ◽  
Bacterial Toxins ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Innate Immune Cells ◽  
Vaccine Adjuvants ◽  
Qualitative Nature ◽  
Ifn Γ

ABSTRACT The ability of innate immune cells to differentially respond to various bacterial components provides a mechanism by which the acquired immune response may be tailored to specific pathogens. The response of innate immune cells to bacterial components provides regulatory signals to cognate immune cells. These signals include secreted cytokines and costimulatory molecules, and to a large extent they determine the quantitative and qualitative nature of the immune response. In order to determine if innate immune cells can differentially respond to bacterial components, we compared the responses of macrophages to two bacterially derived molecules, cholera toxin (CT) and lipopolysaccharide (LPS). We found that CT and LPS differentially regulated the expression of interleukin-12 (IL-12) and CD80-CD86 but not that of IL-1β. LPS and CT each induced IL-1β expression in macrophages, while only LPS induced IL-12 and only CT induced CD80-CD86. These differences were markedly potentiated in gamma interferon (IFN-γ)-treated macrophages, in which LPS potently induced IL-12 and CD80-CD86 expression. In contrast, IFN-γ treatment had no effect on the expression of IL-1β. These results define a molecular basis for the differential pathogenicities of bacterial toxins and are relevant to the design of vaccine adjuvants able to selectively induce desired types of immunity.

scholarly journals Interferon-γ induces interleukin-6 production by neutrophils via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shuhei Yoshida ◽  
Shunya Yamada ◽  
Kohei Yokose ◽  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
...  
Keyword(s):  
Immune Cells ◽  
Interleukin 6 ◽  
Innate Immune ◽  
Janus Kinase ◽  
Human Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Innate Immune Cells ◽  
Mrna Levels ◽  
Signal Transducer ◽  
Ifn Γ

Abstract Objective Interferon-gamma (IFN-γ) is overexpressed in rheumatoid synovium and thought to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we examined our hypothesis that IFN-γ activates innate immune cells and upregulates inflammatory cytokines. Peripheral blood neutrophils were stimulated with IFN-γ in the presence or absence of Janus kinase (JAK) inhibitors. Interleukin-6 (IL-6) mRNA and protein expression were analyzed using real-time polymerase chain reaction (PCR) method and enzyme-linked immunosorbent assay. Protein phosphorylation of JAKs or STAT1 was assessed by Western blot using phospho-specific antibodies. Results IFN-γ stimulation induces IL-6 expression in protein and mRNA levels in human neutrophils. Furthermore, IFN-γ stimulation induces JAK1/JAK2 phosphorylation and downstream signal transducer and activator of transcription (STAT) 1 phosphorylation in human neutrophils. Although all JAKi, blocked IFN-γ-induced JAK1.2/STAT1 phosphorylation at higher concentrations (100 nM), baricitinib most efficiently inhibited IFN-γ-induced JAK1.2/STAT1 phosphorylation at lower concentrations (≤ 25 nM). Among these JAKi, baricitinib was the most potent regulator for IFN-γ-induced IL-6 production in human neutrophils. Our data indicate that IFN-γ upregulates IL-6 production via the JAK1/2-STAT1 pathway in human innate immune cells. Furthermore, this IFN-γ-mediated IL-6 induction via JAK/STAT was downregulated by JAKi.

scholarly journals Cross-Talk between T Cells and Innate Immune Cells Is Crucial for IFN-γ-Dependent Tumor Rejection

2007 ◽  
Vol 179 (3) ◽  
pp. 1568-1576 ◽  
Author(s):  
Zhiguang Li ◽  
Felicia Pradera ◽  
Thomas Kammertoens ◽  
Bing Li ◽  
Shubai Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Innate Immune ◽  
Tumor Rejection ◽  
Innate Immune Cells ◽  
Ifn Γ

scholarly journals Innate immune cytokine profiling and biomarker identification for outcome in dengue patients

2020 ◽  
Author(s):  
Sai Pallavi Pradeep ◽  
Pooja Hoovina Venkatesh ◽  
Nageswar R. Manchala ◽  
Arjun Vayal Veedu ◽  
Rajani K. Basavaraju ◽  
...  
Keyword(s):  
Immune Cells ◽  
Intracellular Cytokine Staining ◽  
Good Prognosis ◽  
Innate Immune ◽  
Severe Dengue ◽  
Innate Immune Cells ◽  
Strong Correlations ◽  
Tnf Α ◽  
Novel Biomarkers ◽  
Ifn Γ

AbstractBiomarkers of progression to severe dengue are urgently required for effective patient management. Innate immune cells have been implicated in the enhancement of infection and “cytokine storm” associated with dengue severity. Using intracellular cytokine staining and flow cytometry, we observed significantly higher proportions of innate immune cells secreting inflammatory cytokines dominated by IFN-γ and TNF-α at admission associated with good prognosis. Secondary dengue predisposed to severe outcomes. In patients with severe dengue and those with liver impairment, early activation as well as efficient down-regulation of innate responses were compromised. IFN-γ+CD56+CD3+ NKT cells and IL-6+ granulocytes served as novel biomarkers of progression to severity (composite AUC=0.85-0.9). Strong correlations among multiple cytokine-secreting innate cell subsets pointed to coordinated activation of the entire innate immune system by DENV.One Sentence SummaryActivation and efficient attenuation of innate immunity are both compromised in severe dengue.

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