Interactions of Pathogenic Bacteria with Autophagy Systems

Abstract

Autophagy is a conserved cellular degradative pathway that is now established to be a vital part of the host immune response to microbial infection. Autophagy can directly eliminate intracellular pathogens by mediating their delivery to lysosomes. Canonical autophagy is characterized by the formation of a double-membrane autophagosome and the involvement of over 35 autophagy-related proteins (Atgs), including a commonly used autophagosome marker in mammalian cells, LC3. Recent studies have shown that a subset of autophagy components can lead to LC3 conjugation onto phagosomes. This process of LC3-associated phagocytosis (LAP) results in the degradation of the cargo by promoting phagosome fusion with lysosomes. Other components of the autophagy machinery also play roles in immunity that are distinct from the canonical autophagy and LAP pathways. This minireview highlights the complicated relationship between autophagy components and intracellular bacteria, including bacterial targeting mechanisms and the interaction between autophagy and effectors/toxins secreted by bacteria.

Metabolic Adaptation of Neutrophils in Cystic Fibrosis Airways Involves Distinct Shifts in Nutrient Transporter Expression

“…This result is consistent with our observations of a major shift in primary granule exocytosis in the A2 subset (4) and with the recently proposed role for the LC3 protein in granulocyte exocytosis (21). Alternatively, the LC3 protein may be involved in other catabolic functions in these cells, including LC3-associated phagocytosis or even conventional autophagic activity (20,22,23).…”

“…Vigilin has been associated with anabolic activity as a positive regulator of mRNA translation in multiple eukaryotic organisms, including humans (17)(18)(19). Simultaneously to vigilin, we characterized the expression of the LC3 protein, previously linked to multiple catabolic activities, including autophagy, phagocytosis, and the exocytosis of proteolytic enzymes (20)(21)(22)(23). Our results demonstrate significant, distinctive metabolic changes among CF airway neutrophil subsets and suggest an important role for nutrient transporters in the inflammatory process observed in CF airway disease.…”

“…This translocation occurred in both the A1 and A2 subsets of airway neutrophils (7.58-and 4.89-fold compared with blood, Table I). Remarkably, expression of the catabolic protein LC3 (20)(21)(22)(23) was increased markedly in the A2 subset of airway neutrophils (Fig. 7), but it was essentially unchanged in the A1 subset (2.1-fold compared with A1, Table I).…”

Two Human Host Defense Ribonucleases against Mycobacteria, the Eosinophil Cationic Protein (RNase 3) and RNase 7

“…Moreover, the enhanced membrane destabilization activity of the RN3(1-45) peptide (Table 2) may partly rely on its aggregation propensity, where a local peptide self-aggregation at the mycobacterial surface could promote the membrane damage. We can also hypothesize that the induction of bacterial cell agglutination by eosinophil granule protein self-aggregation may trigger in vivo the autophagy path, contributing to mycobacterial clearance inside macrophages (73,74).…”

MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection

“…Accumulating data have revealed the crucial and varied roles of autophagy in human health and disease (2,3). The autophagy pathway plays diverse roles in the immune response to pathogenic infection (4,5). A unique function of autophagy is cell-autonomous elimination of intracellular pathogens, including Mycobacterium tuberculosis (6)(7)(8)(9).…”