ALTERATION OF MACROPHAGE FUNCTION BY A TRYPANOSOMA-CRUZI MEMBRANE MUCIN

Cytokines secreted by macrophages play important roles in the immune r esponse to Trypanosoma cruzi. Here, we report that a purified glycosyl phosphatidylinositol (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-me diated cell adhesion as well as an increase in intracellular Ca2+, whi ch was further augmented by cross-linking the Ag C10-bound surface rec eptors by mAb against Ag C10. Interestingly, Ag C10-treated monocytes secreted IL-1 beta, but not TNF-alpha or IL-12. Moreover, these cells could secrete IL-1 beta, 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 T NF-alpha, but not IL-1 beta, upon LPS activation. These effects were s ubstantially inhibited by neutralizing mAb against Ag C10. These effec ts appeared to take place at the transcriptional level, since mRNA for TNF-alpha, but not that for IL-1 beta, was drastically reduced in LPS -stimulated infected cells treated with Ag C10. Conceivably, inhibitio n of TNF-alpha and IL-12 by T cruzi could be involved in the evasion o f the immune response by this parasite.