The Urokinase Receptor Can Be Induced byBorrelia burgdorferithrough Receptors of the Innate Immune System

Abstract

Monocytic cells exposed toBorrelia burgdorferi, through unknown receptors, overexpress the urokinase receptor (uPAR), a key mediator of the plasminogen activation system. We show that combined blockade of CD14 and TLR2 causes a significant inhibition ofB. burgdorferi-induced uPAR in Mono Mac 6 (MM6) cells. Other pattern recognition receptors tested (CD11b/CD18, the mannose receptor, and theN-formyl-methionyl-leucyl-phenylalanine receptor) did not have demonstrated roles inB. burgdorferi-mediated uPAR induction. We dissected the result for CD14 andTLR2 by investigating the singular contributions of each. Independent functional blockade of CD14 or TLR2 failed to inhibitB. burgdorferi-mediated uPAR induction. 1,25-Dihydroxyvitamin D3differentiation of MM6 cells increased CD14 expression 12-fold but did not augmentB. burgdorferi-mediated uPAR expression. Peritoneal exudate macrophages (PEM) from CD14- or TLR2-deficient mice were not defective inB. burgdorferi-mediated synthesis of uPAR mRNA and protein. Increased uPAR mRNA or protein or both were apparent in PEM from transgenic and control mice, even at a ratio of oneBorreliaspirochete per cell. We conclude that signaling for the uPAR response, as mediated byB. burgdorferi, proceeds with CD14 and TLR2 as partial contributors. That part under control of CD14 and TLR2 represents a new link between the host plasminogen activation and innate immunity systems.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady