Mycobacterium tuberculosis Lipoarabinomannan Activates Human Neutrophils via a TLR2/1 Mechanism Distinct from Pam3CSK4.

Mycobacterium tuberculosis Lipoarabinomannan Activates Human Neutrophils via a TLR2/1 Mechanism Distinct from Pam3CSK4. J Immunol. 2019 Dec 23;: Authors: Hook JS, Cao M, Weng K, Kinnare N, Moreland JG 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, M...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research