Alteration of macrophage function by a Trypanosoma cruzi membrane mucin.
Cytokines secreted by macrophages play important roles in the immune response to Trypanosoma cruzi. Here, we report that a purified glycosylphosphatidylinositol (GPI)-anchored mucin from the T. cruzi membrane, Ag C10, is able to bind to the macrophage cell surface and blocks the subsequent binding of mAb against CD62L/L-selectin, whereas binding of mAbs directed against other monocyte surface molecules is unaffected. In addition, Ag C10 binding to macrophages triggered a CD54/ICAM-1-mediated cell adhesion as well as an increase in intracellular Ca2+, which was further augmented by cross-linking the Ag C10-bound surface receptors by mAb against Ag C10. Interestingly, Ag C10-treated monocytes secreted IL-1beta, but not TNF-alpha or IL-12. Moreover, these cells could secrete IL-1beta, but not TNF-alpha or IL-12, after activation with LPS. T. cruzi-infected macrophages displayed similar alterations in cytokine secretion, with an impaired ability to secrete IL-12 and TNF-alpha, but not IL-1beta, upon LPS activation. These effects were substantially inhibited by neutralizing mAb against Ag C10. These effects appeared to take place at the transcriptional level, since mRNA for TNF-alpha, but not that for IL-1beta, was drastically reduced in LPS-stimulated infected cells treated with Ag C10. Conceivably, inhibition of TNF-alpha and IL-12 by T. cruzi could be involved in the evasion of the immune response by this parasite.
de Diego
J
J
Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Punzón
C
C
Duarte
M
M
Fresno
M
M
D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D009000:Monocytes; D009077:Mucins / Q000276:immunology / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000953:Antigens, Protozoan; D016207:Cytokines; D009077:Mucins