Type 3 secretion system induced leukotriene B4 synthesis by leukocytes is actively inhibited by Yersinia pestis to evade early immune recognition.

Autor: Brady A; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Sheneman KR; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Pulsifer AR; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Price SL; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Garrison TM; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Maddipati KR; Department of Pathology, Lipidomics Core Facility, Wayne State University, Detroit, Michigan, United States of America., Bodduluri SR; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Pan J; Biostatistics and Bioinformatics Facility, Brown Cancer Center, University of Louisville, Louisville, Kentucky, United States of America., Boyd NL; Center for Cardiometabolic Science, Christina Lee Brown Environment Institute, Division of Environmental Medicine, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Zheng JJ; Center for Cardiometabolic Science, Christina Lee Brown Environment Institute, Division of Environmental Medicine, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Rai SN; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Hellmann J; Center for Cardiometabolic Science, Christina Lee Brown Environment Institute, Division of Environmental Medicine, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Haribabu B; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America., Uriarte SM; Deptartment of Oral Immunology & Infectious Diseases, University of Louisville, Louisville, Kentucky, United States of America., Lawrenz MB; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, Louisville, Kentucky, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jan 25; Vol. 20 (1), pp. e1011280. Date of Electronic Publication: 2024 Jan 25 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1011280
Abstrakt: Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Brady et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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