Autophagy and inflammatory cell death, partners of innate immunity - PubMed (original) (raw)

Autophagy and inflammatory cell death, partners of innate immunity

Michele S Swanson et al. Autophagy. 2005 Oct-Dec.

Abstract

By law in the evolutionary jungle, any host defense mechanism that efficiently kills microbes also exerts a strong selective pressure for tolerant variants to emerge. As a consequence, pathogens can be exploited as powerful tools to examine host defense mechanisms. Recent studies of the confrontation between macrophages and the opportunistic pathogen Legionella pneumophila have revealed a regulatory mechanism that may link autophagy to pyroptosis, a type of programmed cell death. Building from the extensive literature on autophagy, cell death, and innate immunity, we propose here a testable model in which the NOD-LRR protein Naip5 dictates whether murine macrophages elevate autophagy or pyroptosis as a barrier to infection.

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Figure 1

Figure 1

A model in which Naip5 links autophagy and pyroptosis, two innate immune responses to intracellular pathogens. When ingested by macrophages, Legionella translocate proteins into the host cytoplasm by type IV secretion. When contamination is detected by the Naip5 NOD-LRR protein system, inflammasome assembly activates caspase 1. When caspase 1 levels are low, autophagy captures the microbe for delivery to the degradative lysosomes. When autophagy cannot contain the infection, macrophages initiate pyroptosis, a pro-inflammatory death that recruits leukocytes to the site.

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