Neisseria meningitidis-mediates proinflammatory responses in PMN: Crosstalk TLR-2/c-JunN-Terminal Kinase

Yanyan Xu; Hanan Slimani; Klaus Fersching, Edward Mark, Thomas Baumbusch, Robert Tanaka, Daniel Jakobsson, Min Lee

AJBM  Volume 2, Issue 3, pages 350–363, March 2014             Full Text-PDF


Abstract

Neisseria meningitidis is a Gram-negative bacterium emerging the leading cause of bacterial meningitis in children and young adult wide world. The host innate immune response against meningitis is largely unknown. In this study, we show that N.meningitidis robustly activates mRNA and protein expression of tumor necrosis factor (TNF-α) and interleukin (IL-6) in murine bone marrow-derived PMN. Toll-like receptor (TLR-2) and myeloid differentiation primary response gene 88 (MyD88), N.meningitidis also activates the mitogen-activated protein kinase (MAPKs; c-Jun N-terminal kinase (JNK), ERK1/2 and p38 MAPK) pathway. N.meningitidis-induced TNF-α and IL-6 production was dependent on JNK activation. The intracellular reactive oxygen species (ROS), NADPH oxidase-2, and nuclear factor-κB are required for N.meningitides-induced proinflammatory cytokine generation in PMN. Together, we have demonstrated that N.meningitidis-induced activation of host proinflammatory cytokines is mediated through TLR2-dependent JNK signaling pathways.

Keywords:  N. meningitidis, PMN, TLR, Proinflammatory cytokines, JNK, MyD88


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