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Autophagy is originally described as the main catabolic pathway responsible for maintaining intracellular nutritional homeosta-sis that involves the formation of a unique vacuole, the autophago-some, and the interaction with the endosome-lysosome pathways. This conserved machinery plays a key role in immune-protection against different invaders, including pathogenic bacteria, intracellular parasites, and some viruses like herpes simplex and hepatitis C virus. Importantly, autophagy is linked to a number of human diseases and disorders including neurodegenerative disease, Crohn’s disease, type II diabetes, tumorigenesis, cardiomyopathy, and fatty liver disease. On the other hand, inflammasomes are multiprotein platforms stimulated upon several environmental conditions and microbial infection. Once assembled, the inflammasomes mediate the maturation of pro-inflammatory cytokines and promote phagosome-lysosome fusion to sustain an innate immune response. The intersections between autophagy and inflammasome have been observed in various diseases and microbial infections. This review highlights the molecular aspects involved in autophagy and inflammasome interactions during different medical conditions and microbial infections.

Legionella pneumophila (L. pneumophila) is an intracellular bacterium of human alveolar macrophages that causes Legionnaires' disease. In contrast to humans, most inbred mouse strains are restrictive to L. pneumophila replication. We demonstrate that autophagy targets L. pneumophila vacuoles to lysosomes and that this process requires ubiquitination of L. pneumophila vacuoles and the subsequent binding of the autophagic adaptor p62/SQSTM1 to ubiquitinated vacuoles. The L. pneumophila legA9 encodes for an ankyrin-containing protein with unknown role. We show that the legA9 mutant replicate in WT mice and their bone marrow-derived macrophages. This is the first L. pneumophila mutant to be found to replicate in WT bone marrow-derived macrophages other than the Fla mutant. Less legA9 mutant-containing vacuoles acquired ubiquitin labeling and p62/SQSTM1 staining, evading autophagy uptake and avoiding lysosomal fusion. Thus, we describe a bacterial protein that targets the L. pneumophila-containing vacuole for autophagy uptake.

Influenza A viruses cause a highly-contagious respiratory disease associated with significant morbidity and mortality. The purpose of this study was to utilize F508del CFTR-heterozygous mice to determine the contribution of CFTR-mediated Cl- secretion to influenza pathogenesis and to evaluate CFTR as a therapeutic target. F508del CFTR-heterozygous progeny (HETs) and wild-type (WT) littermate controls were infected intranasally with 50 μl virus diluent (mock) or with 10,000 FFU/mouse influenza A/WSN/33 (H1N1) for 1-6 days. Body weight, lung mechanics, cardiopulmonary function and levels of pulmonary inflammatory mediators were determined over the time of disease. Relative to WT littermate controls, infection-induced hypoxemia and bradycardia were attenuated in HETs at 2-6 days post-infection (d.p.i.), although weight loss and viral replication did not differ. At 2 and 6 d.p.i., alterations in lung function in infected WT mice were absent in HETs at both 2 and 6 d.p.i. Bronchoalveolar lavage fluid from infl...

Clearance of Legionella pneumophila (Legionella), the causative agent of Legionnaire’s disease, a potentially fatal pneumonia, requires efficient phagolysosomal fusion. Regulation of the host actin...