Mucin AgC10 from Trypanosoma cruzi Interferes with L-selectin-mediated monocyte adhesion.
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.
Alcaide
Pilar
P
Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Lim
Yaw Chin
YC
Luscinskas
Francis W
FW
Fresno
Manuel
M
D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D019041:L-Selectin / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology*; D009077:Mucins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D055815:Young Adult
D000953:Antigens, Protozoan; D009077:Mucins; D019041:L-Selectin