Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach.

Autor: Pulsifer AR; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA., Vashishta A; Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA., Reeves SA; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA., Wolfe JK; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, USA., Palace SG; Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Proulx MK; Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Goguen J; Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Bodduluri SR; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Haribabu B; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.; James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA., Uriarte SM; Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA., Lawrenz MB; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA matt.lawrenz@louisville.edu.; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Jazyk: angličtina
Zdroj: Infection and immunity [Infect Immun] 2020 Feb 20; Vol. 88 (3). Date of Electronic Publication: 2020 Feb 20 (Print Publication: 2020).
DOI: 10.1128/IAI.00909-19
Abstrakt: Yersinia pestis causes a rapid, lethal disease referred to as plague. Y. pestis actively inhibits the innate immune system to generate a noninflammatory environment during early stages of infection to promote colonization. The ability of Y. pestis to create this early noninflammatory environment is in part due to the action of seven Yop effector proteins that are directly injected into host cells via a type 3 secretion system (T3SS). While each Yop effector interacts with specific host proteins to inhibit their function, several Yop effectors either target the same host protein or inhibit converging signaling pathways, leading to functional redundancy. Previous work established that Y. pestis uses the T3SS to inhibit neutrophil respiratory burst, phagocytosis, and release of inflammatory cytokines. Here, we show that Y. pestis also inhibits release of granules in a T3SS-dependent manner. Moreover, using a gain-of-function approach, we discovered previously hidden contributions of YpkA and YopJ to inhibition and that cooperative actions by multiple Yop effectors are required to effectively inhibit degranulation. Independent from degranulation, we also show that multiple Yop effectors can inhibit synthesis of leukotriene B 4 (LTB 4 ), a potent lipid mediator released by neutrophils early during infection to promote inflammation. Together, inhibition of these two arms of the neutrophil response likely contributes to the noninflammatory environment needed for Y. pestis colonization and proliferation.
(Copyright © 2020 American Society for Microbiology.)
Databáze: MEDLINE
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