Hemozoin is a key factor in the induction of malaria-associated immunosuppression

Infection-associated immunoincompetence during malaria might result from ma crophage dysfunction. In the present study, we investigated the role of mac rophages as target for immunosuppression during infection, using the murine Plasmodium c. chabaudi model. Special attention has been paid to the analy sis of processing/presentation of protein antigens and presentation of pept ides, using cocultures of peritoneal exudate cells (PECs) from infected mic e and antigen-specific T-cell hybridomas. The results obtained indicate a d efective processing of protein antigens that becomes maximal at acute paras itemias. In addition, macrophages from acutely infected mice suppress the i nterleukin-2 production by the antigen-activated T-cell hybridomas. This ef fect was independent of prostaglandin and nitric oxide production by the ma crophage. The possible role of parasite components in the impaired accessor y cell function of PECs was investigated and hemozoin, the end-product of t he hemoglobin catabolism by intraerythrocytic malaria parasites, was found to induce similar infection-associated deficiencies in vitro. Moreover, hem ozoin, was shown to mimic the immunosuppressive effects induced in PECs dur ing in-vivo infections with P. chabaudi. In conclusion, we propose that hem ozoin is a key factor in the malaria-associated immunosuppression, affectin g both the antigen processing and immunomodulatory functions of macrophages .