Hemolysin Induces Toll-like Receptor (TLR)-independent Apoptosis and Multiple TLR-associated Parallel Activation of Macrophages

作者：Chakraborty Deep Chandan; Mukherjee Gayatri; Banerjee Pallavi; Banerjee Kalyan K; Biswas Tapas^*

来源：Journal of Biological Chemistry, 2011, 286(40): 34542-34551.

DOI：10.1074/jbc.M111.241851

Vibrio cholerae hemolysin (HlyA) displays bipartite property while supervising macrophages (M Phi). The pore-forming toxin causes profound apoptosis within 3h of exposure and in parallel supports activation of the defying M Phi. HlyA-induced apoptosis of M Phi remains steady for 24 h, is Toll-like receptor (TLR)-independent, and is driven by caspase-9 and caspase-7, thus involving the mitochondrial or intrinsic pathway. Cell activation is carried forward by time dependent up-regulation of varying TLRs. The promiscuous TLR association of HlyA prompted investigation, which revealed the beta-prism lectin domain of HlyA simulated TLR4 up-regulation by jacalin, a plant lectin homologue besides expressing CD86 and type I cytokines TNF-alpha and IL-12. However, HlyA cytolytic protein domain up-regulated TLR2, which controlled CD40 for continuity of cell activation. Expression of TOLLIP before TLR2 and TLR6 abrogated TLR4, CD40, and CD86. We show that the transient expression of TOLLIP leading to curbing of activation-associated capabilities is a plausible feedback mechanism of M Phi to deploy TLR2 and prolong activation involving CD40 to encounter the HlyA cytolysin domain.

• 出版日期2011-10-7
• 单位常州工学院