Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection

J Immunol. 2015 Jun 15;194(12):6035-44. doi: 10.4049/jimmunol.1402521. Epub 2015 May 8.


Basic leucine zipper transcription factor Batf2 is poorly described, whereas Batf and Batf3 have been shown to play essential roles in dendritic cell, T cell, and B cell development and regulation. Batf2 was drastically induced in IFN-γ-activated classical macrophages (M1) compared with unstimulated or IL-4-activated alternative macrophages (M2). Batf2 knockdown experiments from IFN-γ-activated macrophages and subsequent expression profiling demonstrated important roles for regulation of immune responses, inducing inflammatory and host-protective genes Tnf, Ccl5, and Nos2. Mycobacterium tuberculosis (Beijing strain HN878)-infected macrophages further induced Batf2 and augmented host-protective Batf2-dependent genes, particularly in M1, whose mechanism was suggested to be mediated through both TLR2 and TLR4 by LPS and heat-killed HN878 (HKTB) stimulation experiments. Irf1 binding motif was enriched in the promoters of Batf2-regulated genes. Coimmunoprecipitation study demonstrated Batf2 association with Irf1. Furthermore, Irf1 knockdown showed downregulation of IFN-γ- or LPS/HKTB-activated host-protective genes Tnf, Ccl5, Il12b, and Nos2. Conclusively, Batf2 is an activation marker gene for M1 involved in gene regulation of IFN-γ-activated classical macrophages, as well as LPS/HKTB-induced macrophage stimulation, possibly by Batf2/Irf1 gene induction. Taken together, these results underline the role of Batf2/Irf1 in inducing inflammatory responses in M. tuberculosis infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cluster Analysis
  • Disease Models, Animal
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Knockdown Techniques
  • Interferon Regulatory Factor-1 / genetics*
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / immunology
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mycobacterium / immunology*
  • Mycobacterium Infections / genetics*
  • Mycobacterium Infections / immunology*
  • Mycobacterium Infections / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Protein Binding
  • Tumor Necrosis Factors / genetics
  • Tumor Necrosis Factors / metabolism


  • BATF2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Interferon Regulatory Factor-1
  • Lipopolysaccharides
  • Tumor Necrosis Factors
  • Interferon-gamma
  • Nitric Oxide Synthase Type II

Associated data

  • GEO/GSE59210