Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

Abstract

Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

Autophagy in sepsis: Degradation into exhaustion?

“…Supporting this notion, overexpression of LC3 can successfully restore the autophagic insufficiency in septic lung. 52 Given multiple roles of autophagy in microbial clearance, 70 neutralizing microbial toxins, 71 maintaining mitochondrial integrity 46 and controlling cytokine release, 32 suppression of the process would likely lead to poor outcome in sepsis. The progression of sepsis into immunosuppression may be explained by the role of autophagy in maintaining survival and proliferation of T-lymphocytes.…”

“…5 Despite this robust degradation, certain microbes could express virulence factors, which either stall autophagosomelysosome fusion or inhibit the initiation of autophagosome formation. 2,5,70 The role of autophagy in sepsis is also dependent on bacterial factors. Inoculation of wild-type Staphylococcus aureus strain USA300 confers higher mortality rate in lc3b ¡/¡ and ATG16L1 hypomorphic mice as compared to wild-type groups.…”

“…Conversely, administration of a-toxin-deleted S. aureus USA300 protects ATG16L1-deficient mice against sepsis. 70 Interestingly, deletion of Atg16l1 in endothelial cells is more lethal than that in macrophages or dendritic cells. 68 The interaction between bacteria and autophagy, or xenophagy, has been comprehensively reviewed by Huang and colleagues.…”

Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations

“…Antibodies might thus trigger non-selective autophagy, thus leading to the clearance of α-syn through a non α-syn-related mechanism. Indeed autophagy might be unselectively activated as part of an innate immune response against pathogens, here the presence of antibodies 109 ; thus leading to the clearance of α-syn through a non-α-syn-related mechanism. The use of intrabodies, that are gene-engineered antibodies specifically built for acting intracellularly, might be more specific 110 .…”

Pseudorabies virus infection inhibits autophagy in permissive cells in vitro

“…Conversely, autophagy can be an antiviral defense mechanism. The term xenophagy describes the process through which the autophagy machinery protects eukaryotes from infection14. Activation of the autophagic pathway can effectively eliminate intracellular pathogens by fusing with lysosomes, which has been observed for bacteria, such as Mycobacterium tuberculosis 1516, and viruses, such as tobacco mosaic virus17 and herpes simplex virus18.…”