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  • IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes.

IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes.

Nature communications (2015-03-17)
Monica Gupta, Dong-Mi Shin, Lakshmi Ramakrishna, Dennis J Goussetis, Leonidas C Platanias, Huabao Xiong, Herbert C Morse, Keiko Ozato
ABSTRACT

Autophagy, activated by many stresses, plays a critical role in innate immune responses. Here we show that interferon regulatory factor 8 (IRF8) is required for the expression of autophagy-related genes in dendritic cells. Furthermore in macrophages, IRF8 is induced by multiple autophagy-inducing stresses, including IFNγ and Toll-like receptor stimulation, bacterial infection, starvation and by macrophage colony-stimulating factor. IRF8 directly activates many genes involved in various steps of autophagy, promoting autophagosome formation and lysosomal fusion. Consequently, Irf8(-/-) macrophages are deficient in autophagic activity, and excessively accumulate SQSTM1 and ubiquitin-bound proteins. We show that clearance of Listeria monocytogenes in macrophages requires IRF8-dependent activation of autophagy genes and subsequent autophagic capturing and degradation of Listeria antigens. These processes are defective in Irf8(-/-) macrophages where uninhibited bacterial growth ensues. Together these data suggest that IRF8 is a major autophagy regulator in macrophages, essential for macrophage maturation, survival and innate immune responses.

MATERIALS
Product Number
Brand
Product Description

Millipore
Brain Heart Infusion Agar, suitable for microbiology, NutriSelect® Plus, For the cultivation of fastidious, pathogenic bacteria, yeasts, and molds
Sigma-Aldrich
Dansylcadaverine, suitable for fluorescence, BioReagent, ≥99.0% (HPLC)
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ~98% (HPLC)