Cell death and infection: A double-edged sword for host and pathogen survival

Host cell death is an intrinsic immune defense mechanism in response to microbial infection. However, bacterial pathogens use many strategies to manipulate the host cell death and survival pathways to enhance their replication and survival. This manipulation is quite intricate, with pathogens often suppressing cell death to allow replication and then promoting it for dissemination. Frequently, these effects are exerted through modulation of the mitochondrial pro-death, NF-κB–dependent pro-survival, and inflammasome-dependent host cell death pathways during infection. Understanding the molecular details by which bacterial pathogens manipulate cell death pathways will provide insight into new therapeutic approaches to control infection.

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UropathogenicEscherichia coliEpigenetically Manipulate Host Cell Death Pathways

The Journal of Infectious Diseases ◽

10.1093/infdis/jiv569 ◽

2015 ◽

Vol 213 (7) ◽

pp. 1198-1207 ◽

Cited By ~ 8

Author(s):

Zhengguo Zhang ◽

Ming Wang ◽

Florian Eisel ◽

Svetlin Tchatalbachev ◽

Trinad Chakraborty ◽

...

Keyword(s):

Cell Death ◽

Host Cell ◽

Cell Death Pathways ◽

Host Cell Death

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

Pathogens ◽

10.3390/pathogens7010008 ◽

2018 ◽

Vol 7 (1) ◽

pp. 8 ◽

Cited By ~ 8

Author(s):

Courtney McDougal ◽

John-Demian Sauer

Keyword(s):

Cell Death ◽

Listeria Monocytogenes ◽

Host Cell ◽

Acute Infection ◽

Host Cells ◽

Cell Mediated Immunity ◽

Cell Death Pathways ◽

Host Cell Death ◽

The Impact

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.

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Interaction of Mycobacterium tuberculosis with Host Cell Death Pathways

Cold Spring Harbor Perspectives in Medicine ◽

10.1101/cshperspect.a022459 ◽

2014 ◽

Vol 4 (8) ◽

pp. a022459-a022459 ◽

Cited By ~ 33

Author(s):

L. Srinivasan ◽

S. Ahlbrand ◽

V. Briken

Keyword(s):

Cell Death ◽

Mycobacterium Tuberculosis ◽

Host Cell ◽

Cell Death Pathways ◽

Host Cell Death

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Selective Host Cell Death by Staphylococcus aureus: A Strategy for Bacterial Persistence

Frontiers in Immunology ◽

10.3389/fimmu.2020.621733 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dominique Missiakas ◽

Volker Winstel

Keyword(s):

Staphylococcus Aureus ◽

Cell Death ◽

Host Cell ◽

Intervention Strategies ◽

Host Cells ◽

Intracellular Killing ◽

Mammalian Development ◽

Cell Responses ◽

Cell Death Pathways ◽

Host Cell Death

Host cell death programs are fundamental processes that shape cellular homeostasis, embryonic development, and tissue regeneration. Death signaling and downstream host cell responses are not only critical to guide mammalian development, they often act as terminal responses to invading pathogens. Here, we briefly review and contrast how invading pathogens and specifically Staphylococcus aureus manipulate apoptotic, necroptotic, and pyroptotic cell death modes to establish infection. Rather than invading host cells, S. aureus subverts these cells to produce diffusible molecules that cause death of neighboring hematopoietic cells and thus shapes an immune environment conducive to persistence. The exploitation of cell death pathways by S. aureus is yet another virulence strategy that must be juxtaposed to mechanisms of immune evasion, autophagy escape, and tolerance to intracellular killing, and brings us closer to the true portrait of this pathogen for the design of effective therapeutics and intervention strategies.

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Inflammasomes, Autophagy, and Cell Death: The Trinity of Innate Host Defense against Intracellular Bacteria

Mediators of Inflammation ◽

10.1155/2019/2471215 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 20

Author(s):

Teresa Krakauer

Keyword(s):

Cell Death ◽

Host Cell ◽

Host Defense ◽

Intracellular Bacteria ◽

Inflammasome Activation ◽

Type I ◽

Dependent Manner ◽

Cell Death Pathways ◽

Host Cell Death ◽

Molecular Patterns

Inflammasome activation is an innate host defense mechanism initiated upon sensing pathogens or danger in the cytosol. Both autophagy and cell death are cell autonomous processes important in development, as well as in host defense against intracellular bacteria. Inflammasome, autophagy, and cell death pathways can be activated by pathogens, pathogen-associated molecular patterns (PAMPs), cell stress, and host-derived damage-associated molecular patterns (DAMPs). Phagocytosis and toll-like receptor (TLR) signaling induce reactive oxygen species (ROS), type I IFN, NFκB activation of proinflammatory cytokines, and the mitogen-activated protein kinase cascade. ROS and IFNγare also prominent inducers of autophagy. Pathogens, PAMPs, and DAMPs activate TLRs and intracellular inflammasomes, inducing apoptotic and inflammatory caspases in a context-dependent manner to promote various forms of cell death to eliminate pathogens. Common downstream signaling molecules of inflammasomes, autophagy, and cell death pathways interact to initiate appropriate measures against pathogens and determine host survival as well as pathological consequences of infection. The integration of inflammasome activation, autophagy, and cell death is central to pathogen clearance. Various pathogens produce virulence factors to control inflammasomes, subvert autophagy, and modulate host cell death in order to evade host defense. This review highlights the interaction of inflammasomes, autophagy, and host cell death pathways in counteractingBurkholderia pseudomallei, the causative agent of melioidosis. Contrasting evasion strategies used byB.pseudomallei,Mycobacterium tuberculosis, andLegionella pneumophilato avoid and dampen these innate immune responses will be discussed.

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