Role of cell membrane receptors in the suppression of monocyte anti-microbial activity against Mycobacterium avium subsp paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP), the agent of paratuberculosis, is a slow growing mycobacteria that survives within ruminant mononuclear phagocytes by preventing cell activation and phagosome maturation. We investigated interactions between MAP and monocyte membrane receptors that result in activation of the mitogen-activated protein kinase (MAPK) p38 pathway and suppression of monocyte antimicrobial activity, Bovine monocytes were treated with blocking antibodies or specific chemical inhibitors of toll-like receptor 2 (TLR2), CD14 and CR3 receptor before infection with MAP organisms. MAPKp38 pathway activation, IL-10 expression and production, phagosome acidification, and MAP Survival were determined. Our results indicated that MAP organisms-induced MAPKp38 activation occurs through partial interaction with TLR2. Blocking TLR2 receptors decreased IL-10 mRNA expression but not IL-10 protein production, increased phagosome acidification, and increased the capacity of monocytes to kill MAP organisms. Furthermore, blocking CR3 receptors increased phagosome acidification but did not alter MAP killing. These finding suggest that phagosome acidification is dependent on a complex interaction between MAP and the phagosome wall that may involve multiple receptors but that organism killing is dependent on specific signaling involving TLR2 receptors. (C) 2007 Elsevier Ltd. All rights reserved.