التفاصيل البيبلوغرافية
| العنوان: |
Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages. |
| المؤلفون: |
Brady, Amanda1 (AUTHOR), Mora Martinez, Leonardo C.1 (AUTHOR), Hammond, Benjamin1 (AUTHOR), Whitefoot-Keliin, Kaitlyn M.1 (AUTHOR), Haribabu, Bodduluri1,2 (AUTHOR), Uriarte, Silvia M.3,4 (AUTHOR), Lawrenz, Matthew B.1,4 (AUTHOR) matt.lawrenz@louisville.edu |
| المصدر: |
PLoS Pathogens. 10/18/2024, Vol. 20 Issue 10, p1-23. 23p. |
| مصطلحات موضوعية: |
*YERSINIA pestis, *SECRETION, *MITOGEN-activated protein kinases, *CASCADE control, *IMMUNE recognition, *PHAGOCYTOSIS |
| مستخلص: |
Leukotriene B4 (LTB4) is an inflammatory lipid produced in response to pathogens that is critical for initiating the inflammatory cascade needed to control infection. However, during plague, Yersinia pestis inhibits the timely synthesis of LTB4 and subsequent inflammation. Using bacterial mutants, we previously determined that Y. pestis inhibits LTB4 synthesis via the action of the Yop effector proteins that are directly secreted into host cells through a type 3 secretion system (T3SS). Here, we show that the T3SS is the primary pathogen associated molecular pattern (PAMP) required for production of LTB4 in response to both Yersinia and Salmonella. However, we also unexpectantly discovered that T3SS-mediated LTB4 synthesis by neutrophils and macrophages require the activation of two distinctly different host signaling pathways. We identified that phagocytosis and the NLRP3/CASP1 inflammasome significantly impact LTB4 synthesis by macrophages but not neutrophils. Instead, the SKAP2/PLC signaling pathway is required for T3SS-mediated LTB4 production by neutrophils. Finally, while recognition of the T3SS is required for LTB4 production, we also discovered that a second unrelated PAMP-mediated signal activates the MAP kinase pathway needed for synthesis. Together, these data demonstrate significant differences in the host factors and signaling pathways required by macrophages and neutrophils to quickly produce LTB4 in response to bacteria. Moreover, while macrophages and neutrophils might rely on different signaling pathways for T3SS-dependent LTB4 synthesis, Y. pestis has evolved virulence mechanisms to counteract this response by either leukocyte to inhibit LTB4 synthesis and colonize the host. Author summary: The production of inflammatory lipid mediators by the host is essential for timely inflammation in response to invasion by bacterial pathogens. Therefore, defining how immune cells recognize pathogens and rapidly produce these lipids is essential for us to understand how our immune system effectively controls infection. In this study, we discovered that the host signaling pathways required for leukotriene B4 (LTB4) synthesis differ between neutrophils and macrophages, highlighting important differences in how immune cells respond to infection. Together, these data represent a significant improvement in our understanding of how neutrophils and macrophages rapidly react to bacteria and provide new insights into how Yersinia pestis manipulates leukocytes to evade immune recognition to cause disease. [ABSTRACT FROM AUTHOR] |
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