Listeria monocytogenes: The Impact of Cell Death on Infection and Immunity

Abstract

Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications on the development of disease and the subsequent immune response. Although L. monocytogenes can activate multiple pathways of host cell death, including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens L. monocytogenes has evolved a series of adaptations that minimize host cell death to promote its virulence. Understanding how L. monocytogenes modulates cell death during infection could lead to novel therapeutic approaches. In addition, as L. monocytogenes is currently being developed as a tumor immunotherapy platform, understanding how cell death pathways influence the priming and quality of cell-mediated immunity is critical. This review will focus on the mechanisms by which L. monocytogenes modulates cell death, as well as the implications of cell death on acute infection and the generation of adaptive immunity.

Why isListeria monocytogenessuch a potent inducer of CD8+ T‐cells?

“…Many bacterial pathogens induce pyroptosis, although it typically plays only modest roles in host resistance to infection, probably because bona fide pathogens evolve to avoid it (Jorgensen & Miao, ). L. monocytogenes infection of BMMs results in relatively low levels of pyroptosis, but that which occurs is mostly due to the infrequent lysis of cytosolic bacteria and the activation of the DNA‐dependent AIM2 inflammasome (McDougal & Sauer, ). In addition, LLO, like other pore‐forming toxins, can activate the NLRP3 inflammasome, but this occurs from the outside of cells and probably is not directly relevant to L. monocytogenes pathogenesis (Sauer et al, ).…”

“…The simplest explanation is that premature killing of the APCs prevents all aspects of immunity including secretion of cytokines and presenting of antigen. However, infected host cell death does not preclude that killed cells are phagocytosed by DCs and processed by cross‐presentation (Alloatti, Kotsias, Magalhaes, & Amigorena, ; Edelson, ), and indeed, although CMI is diminished, there remains substantial levels of immunity in mice immunised with cytotoxic strains (McDougal & Sauer, ; Sauer, Pereyre, et al, ).…”

Attenuation of Listeria monocytogenes Virulence by Cannabis sativa L. Essential Oil

“…Infection of the human host is commonly via the oral route, through ingestion of contaminated food, although transplacental transmission during gestation also occurs. Severe L. monocytogenes infection include septicaemia, meningitis, endocarditis, and spontaneous abortion (McDougal and Sauer, 2018 ). Infection requires bacterial internalization into host cells, intracellular survival, and spread into neighboring cells, which enable bacterial diffusion from the primary site of infection, usually the bowel, to the liver, the spleen, and on to peripheral blood and eventually the brain.…”

PANoptosis in microbial infection

“…Loss of these effectors consequently may allow for increased activation of PANoptosis [ 34 , 35 , 36 ]. Other bacteria, including Listeria monocytogenes and Francisella novicida , also have the potential to activate multiple cell death processes [ 15 •• , 37 , 38 ]. Francisella infection activates the AIM2 inflammasome, and recent studies have identified that AIM2, through ASC, can also promote apoptosis via caspase-8 [ 39 ].…”