Interferon Regulatory Factor 8 (IRF8) is a master regulator of Autophagy in bone marrow derived macrophage & promotes the clearance of self and viral proteins

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NICHD	IMMUNO-9

Authors

• M Gupta
• DM Shin
• L Ramakrishna
• HC Morse
• K Ozato

Abstract

Autophagy plays a pivotal role in innate and adaptive immunity. It is involved in the clearance of intracellular organisms in macrophages. Factors involved in the regulation of autophagy in macrophages cells are not understood. In the present study we found that Interferon Regulatory Factor 8 (IRF8), a transcription factor essential for myeloid cell function, plays a critical role in the full execution of interferon γ (IFNγ)/Toll like receptor (TLR) signal induced autophagy in macrophages. Our analysis revealed that in response to IFNγ & TLR stimulation, the expression of crucial autophagy-related genes are induced in WT macrophages but not in IRF8-/- cells. The expression of the above genes in IRF8-/- cells can be rescued by IRF8 gene transfer. Autophagosomes, a unique structure formed during autophagy, increases in the WT cells w.r.t stimulation but not in IRF8-/- macrophages. Furthermore, intracellular degradation of ubiquitinated proteins is defective in IRF8-/- macrophages. In IRF 8-/- cells intracellular clearance of retroviral particles is impaired as compared to the WT cells. The protein expressed by viruses is localized in the inclusion bodies in IRF 8-/- macrophages whereas in WT cells it is localized within the autophagosomes, explaining the reason behind the virus clearance in the latter cells.

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