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- W2998006775 abstract "Neutrophils, polymorphonuclear (PMN) leukocytes, play an important role in the early innate immune response to Mycobacterium tuberculosis infection in the lung. Interactions between PMN and mycobacterial lipids impact the activation state of these migrated cells with consequences for the surrounding tissue in terms of resolution versus ongoing inflammation. We hypothesized that lipoarabinomannan from M. tuberculosis (Mtb LAM) would prime human PMN in a TLR2-dependent manner and investigated this with specific comparison with the purified synthetic TLR2 agonists, Pam3CSK4 and FSL-1. In contrast to Pam3CSK4 and FSL-1, we found Mtb LAM did not induce any of the classical PMN priming phenotypes, including enhancement of NADPH oxidase activity, shedding of l-selectin, or mobilization of CD11b. However, exposure of PMN to Mtb LAM did elicit pro- and anti-inflammatory cytokine production and release in a TLR2/1-dependent manner, using the TLR1 single-nucleotide polymorphism rs5743618 (1805G/T) as a marker for TLR2/1 specificity. Moreover, Mtb LAM did not elicit p38 MAPK phosphorylation or endocytosis, although these processes occurred with Pam3CSK4 stimulation, and were necessary for the early priming events to occur. Interestingly, Mtb LAM did not abrogate priming responses elicited by Pam3CSK4 Notably, subfractionation of light membranes from Pam3CSK4 versus Mtb LAM-stimulated cells demonstrated differential patterns of exocytosis. In summary, Mtb LAM activates PMN via TLR2/1, resulting in the production of cytokines but does not elicit early PMN priming responses, as seen with Pam3CSK4 We speculate that the inability of Mtb LAM to prime PMN may be due to differential localization of TLR2/1 signaling." @default.
- W2998006775 created "2020-01-10" @default.
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- W2998006775 creator A5062902296 @default.
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- W2998006775 date "2019-12-23" @default.
- W2998006775 modified "2023-10-17" @default.
- W2998006775 title "Mycobacterium tuberculosisLipoarabinomannan Activates Human Neutrophils via a TLR2/1 Mechanism Distinct from Pam3CSK4" @default.
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- W2998006775 doi "https://doi.org/10.4049/jimmunol.1900919" @default.
- W2998006775 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31871022" @default.
- W2998006775 hasPublicationYear "2019" @default.
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