Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice

Physiological Reports, Journal Year: 2025, Volume and Issue: 13(3)

Published: Feb. 1, 2025

Influenza infections are often complicated by secondary bacterial such as MRSA pneumonia, which increase morbidity and mortality. Viral lead to an inflammatory response that includes elevated levels of IL-6 interferons. activates the JAK/STAT signaling pathway, amplifying downstream inflammation. Given clinical efficacy JAK inhibitor baricitinib in reducing disease severity COVID-19, we evaluated its impact a murine model influenza, MRSA, post-influenza pneumonia. Additionally, because inhibitory therapies have improved outcomes during deletion on In our studies, effectively inhibited pathway lungs, demonstrated decreased interferon-stimulated genes (ISGs) STAT3 phosphorylation. Despite this inhibition, did not cause global suppression cytokines. Notably, treatment impair either antiviral or antibacterial host immunity, cell recruitment, lung tissue injury. deficiency alter weight loss, burden These findings suggest both inhibition via do enhance defense limit injury models influenza

Language: Английский

Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated Endogenous IFNLR1

Journal of Interferon & Cytokine Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Distinct transcriptional isoforms of the interferon lambda receptor 1 (IFNLR1) are expressed in hepatocytes, but whether corresponding full-length and truncated IFNLR1 protein variants have discrete function is unclear. We quantitated liver blood from individuals with chronic hepatitis C virus (HCV) infection before after antiviral treatment, hypothesizing their relative expression may differentially change during resolution virus-induced inflammation. also FLAG-tagged stem cell-derived hepatocytes (iHeps) abrogated endogenous to evaluate function. decreased treatment HCV, no distinct pattern decline was observed for any individual isoform. Expression enabled (IFNL)-induced proinflammatory genes augmented inhibition B (HBV) replication wild-type (WT) iHeps. A noncanonical variant missing part JAK1 binding domain IFNLs induce could not support induction or HBV beyond that WT iHeps intact IFNLR1. secreted had identified lacking Although did distinctly HCV functional studies suggest titrate versus responses context viral hepatitis.

Language: Английский

An IFN-STAT1-CYBB Axis Defines Protective Plasmacytoid DC to Neutrophil Crosstalk During Aspergillus fumigatus Infection.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), a devastating infection in immunocompromised patients. Plasmacytoid dendritic cells (pDCs) regulate host defense against IA by enhancing neutrophil antifungal properties lung. Here, we define pDC activation trajectory during A. and molecular events that underlie protective - crosstalk. Fungus-induced begins after bone marrow egress results pDC-dependent regulation lung type I III IFN levels. These pDC-derived products act on receptor-expressing neutrophils control fungicidal activity reactive oxygen species production via STAT1 signaling cell-intrinsic manner. Mechanistically, regulates transcription expression Cybb, which encodes one five NADPH oxidase subunits. Thus, pDCs neutrophil-dependent immunity inhaled molds controlling local subunit required for assembly

Language: Английский