Salmonella Interacts With Autophagy to Offense or Defense

Abstract

Autophagy is an important component of the innate immune system in mammals. Low levels of basic autophagy are sustained in normal cells, to help with the clearance of aging organelles and misfolded proteins, thus maintaining their structural and functional stability. However, when cells are faced with challenges, such as starvation or pathogenic infection, their level of autophagy increases significantly. Salmonella is a facultative intracellular pathogen, which imposes an economic burden on the poultry farming industry and human public health. Previous studies have shown that Salmonella can induce the autophagy of cells following invasion, which to a certain extent helps to protect the cells from bacterial colonization. This review summarizes the latest research in the field of Salmonella-induced autophagy, including: (i) the autophagy induction and escape mechanisms employed by Salmonella during the infection of host cells; (ii) the effect of autophagy on intracellular Salmonella; (iii) the important autophagy adaptors that recognize intracellular Salmonella in host cells; and (iv) the effect of autophagy-modulating drugs on Salmonella infection.

Salmonella subverts autophagy balancing bacterial fate and cellular inflammation

“…Autophagy has been well-documented to target and eradicate the cytosolic bacteria via targeting the disrupted cellular membrane structures and ubiquitinated bacteria, serving as one of the host cellular machineries that regulates S. Typhimurium lifestyle (Wu et al, 2020). Autophagy has been implied to restrict cytosolic S. Typhimurium, while independent reports have offered opposite insight on the role of autophagy for S. Typhimurium cytosolic lifestyle.…”

“…Autophagy has been well-documented to target and eradicate the cytosolic bacteria via targeting the disrupted cellular membrane structures and ubiquitinated bacteria, serving as one of the host cellular machineries that regulates S. Typhimurium lifestyle (Wu et al, 2020).…”

“…Recently, the S. Typhimurium effector SopF was reported to maintain SCV integrity and acts on the autophagy system in the context of vacuolar rupture (Lau et al, 2019;Xu et al, 2019). This is relevant as S. Typhimurium released into the host cytosol are first challenged by autophagy degradation, where the escaped S. Typhimurium undertake a fast-growing phenotype, coined hyper replication (Knodler et al, 2010;Wu et al, 2020). The hyper replicating S. Typhimurium in the host cytosol activates the host non-canonical inflammosome, leading to host cell extrusion and pyroptotic death, which releases the invasion-primed hyper replicating S. Typhimurium into the gut lumen.…”

Autophagy—A Story of Bacteria Interfering with the Host Cell Degradation Machinery

“…Here, we will describe some of these mechanisms ( Figure 4 ). The best-studied bacteria regarding autophagy are Salmonella typhimurium [ 74 , 75 ], Mycobacterium tuberculosis [ 75 , 76 ], Legionella pneumophila [ 75 , 77 , 78 ], Listeria monocytogenes [ 75 , 79 ], Coxiella burnetii [ 78 ], and Shigella flexneri [ 75 , 80 ]. Because other reviews have focussed on these bacteria [ 75 , 81 ], we will only provide short summaries of their effects on autophagy here.…”

Anaplasmataceae: Dichotomous Autophagic Interplay for Infection

“…Autophagy receptors such as p62/SQSTM1, nuclear domain 10 protein 52 (NDP52) and neighbor of BRCA1 gene 1 (NBR1) have been shown to bind ubiquitinated intracellular pathogens for autolysosome destruction and clearance (31). Autophagy plays an important role in both innate and adaptive immunity to various intracellular pathogens including Mycobacterium tuberculosis, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella enterica (38)(39)(40)(41)(42).…”