IRF5 regulates airway macrophage metabolic responses.

IRF5 regulates airway macrophage metabolic responses. Clin Exp Immunol. 2021 Jan 10;: Authors: Albers GJ, Iwasaki J, McErlean P, Ogger PP, Ghai P, Khoyratty TE, Udalova IA, Lloyd CM, Byrne AJ Abstract Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage phenotype and a key transcription factor involved in expression of pro-inflammatory cytokine responses to microbial and viral infection. Here, we show that IRF5 controls cellular and metabolic responses. By integrating ChIP-seq and ATAC-seq datasets, we uncovered that IRF5 directly regulates metabolic genes such as hexokinase-2 (Hk2). The interaction of IRF5 and metabolic genes had a functional consequence, since Irf5-/- AMs but not bone marrow derived macrophages (BMDMs) were characterized by a quiescent metabolic phenotype at baseline and had reduced ability to utilize oxidative phosphorylation after TLR3 activation ex vivo. In a murine model of influenza infection, IRF5 deficiency had no effect on viral load in comparison to WT controls, but controlled metabolic responses to viral infection since IRF5 deficiency led to reduced expression of Sirt6 and Hk2. Together, our data indicate that IRF5 is a key component of AM metabolic responses following influenza infection and TLR3 activation. PMID: 33423291 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research