Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

Infection and Immunity
Taylor J SchoberleJames B Bliska

Abstract

Pathogenic Yersinia species utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promote Yersinia pathogenesis. In turn,Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior to Yersinia pseudotuberculosis infection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of aY. pseudotuberculosis yopM mutant was compared to that of a yopJ yopM, yopE yopM, yopH yopM, yopT yopM, or ypkA yopM mutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutant Y. pseudotuberculosis strains. Results show enhanced activati...Continue Reading

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Citations

Nov 9, 2016·Immunology and Cell Biology·Meghan Bliss-MoreauBen A Croker
Dec 3, 2016·PLoS Pathogens·Dmitry RatnerEgil Lien
Jun 28, 2016·F1000Research·Steve Atkinson, Paul Williams
Jul 29, 2020·Immunological Reviews·Haleema S Malik, James B Bliska
Oct 10, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lingfang ZhuXihui Shen

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