Autophagy Protects Against Active Tuberculosis by Suppressing Bacterial Burden and Inflammation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Oct 25

PMID 23093667

Citations 263

Authors

Eliseo F Castillo

Alexander Dekonenko

John Arko-Mensah

Michael A Mandell

Nicolas Dupont

Shanya Jiang

Monica Delgado-Vargas

Graham S Timmins

Dhruva Bhattacharya

Hongliang Yang

Julie Hutt

C Rick Lyons

Karen M Dobos

Vojo Deretic

Affiliations

Soon will be listed here.

Abstract

Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against Mycobacterium tuberculosis, but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. M. tuberculosis infection of Atg5(fl/fl) LysM-Cre(+) mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1α levels. Macrophages from uninfected Atg5(fl/fl) LysM-Cre(+) mice displayed a cell-autonomous IL-1α hypersecretion phenotype, whereas T cells showed propensity toward IL-17 polarization during nonspecific activation or upon restimulation with mycobacterial antigens. Thus, autophagy acts in vivo by suppressing both M. tuberculosis growth and damaging inflammation.

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