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Mucin AgC10 from Trypanosoma cruzi Interferes with L-Selectin-Mediated Monocyte Adhesion

Author:
Alcaide, Pilar, Lim, Yaw Chin, Luscinskas, Francis W., Fresno, Manuel
Source:
Infection and immunity 2010 v.78 no.3 pp. 1260-1268
ISSN:
0019-9567
Subject:
Trypanosoma cruzi, blood flow, endothelium, humans, immune response, mucins, parasites
Abstract:
The protozoan parasite Trypanosoma cruzi has evolved sophisticated systems to evade the immune response. An important requirement for a productive immune response is recruitment of the appropriate immune cells from the bloodstream to the sites of infection. Here, we show that a mucin expressed and secreted by the metacyclic infective form of T. cruzi, AgC10, is able to interfere with L-selectin-mediated monocyte adhesion. Thus, incubation of U937 monocytic cells stably expressing L-selectin (U937LAM) with AgC10 strongly reduced their adhesion on P-selectin under flow, which is dependent on L-selectin. This treatment also results in a significant inhibition by AgC10 of U937LAM and human primary monocyte adhesion to activated vascular endothelium. This effect was specific for L-selectin, because vascular cell adhesion molecule 1 (VCAM-1)-mediated adhesion was not affected by AgC10 pretreatment. This effect of AgC10 is likely due to its ability to induce L-selectin shedding from the monocyte membrane, since pharmacologic blocking of this shedding prevents AgC10 activity. This is the first description of a mechanism that prevents leukocyte adhesion to the endothelium by a parasite and represents a new potential countermeasure to evade the generation of a correct immune response.
Agid:
283524