Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway (Cell, 2012, 150:803-815)

報告日期: 2012/10/09
報告時間: 16:00/16:50
報告學生: 郭承儒
講評老師: 黃一修
附件下載: 下載[1226-1348566936-1.pdf] 

 

Extracellular M. tuberculosis DNA Targets Bacteria for Autophagy by Activating the Host DNA-Sensing Pathway

Robert O. Watson, Paolo S. Manzanillo, and Jeffery S. Cox

                                                    Cell 150, 803–815 (2012)

Speaker:郭承儒                                                        Time2012/10/09  16:00

                            Commentator黃一修老師                                        PlaceRoom 602

Abstract

Autophagy is an evolutionarily conserved intracellular process in eukaryotes whereby bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Two types of macroautophagy have been identified to date. Non-selective autophagy occurs on nutrient limitation to supply cells with essential metabolic building blocks and energy until nutrients can once again be obtained from the extracellular environment. In contrast, selective autophagy occurs under nutrient-rich conditions to mediate the removal of superfluous or damaged organelles and protein aggregates through the use of ubiquitin-mediated targeting that otherwise could be toxic. Autophagy can serve as an intrinsic immune defense against invading intracellular pathogens by eliminating them or their products in a process termed xenophagy, a form of autophagy where foreign rather than self-molecules are targeted for degradation in autophagosomes. 

Mycobacterium tuberculosis which is responsible for several million deaths annually and causes devastating illness in infected individuals is an intracellular pathogen persisting within phagosomes through interference with phagolysosome biogenesis.

In this article, the authors demonstrate that M. tuberculosis cells are recognized by host macrophages and targeted to autophagosomes. Recognition and targeting requires both the type VII secretion system EXS-1-mediated phagosomal permeabilization and the host cytosolic DNA-sensing pathway, STING, revealing a novel link between nucleic acid sensing, innate immunity, and selective autophagy of intracellular pathogens.