Hemozoin is a key factor in the induction of malaria-associated immunosuppression.
Infection-associated immunoincompetence during malaria might result from macrophage dysfunction. In the present study, we investigated the role of macrophages as target for immunosuppression during infection, using the murine Plasmodium c. chabaudi model. Special attention has been paid to the analysis of processing/presentation of protein antigens and presentation of peptides, using cocultures of peritoneal exudate cells (PECs) from infected mice and antigen-specific T-cell hybridomas. The results obtained indicate a defective processing of protein antigens that becomes maximal at acute parasitemias. In addition, macrophages from acutely infected mice suppress the interleukin-2 production by the antigen-activated T-cell hybridomas. This effect was independent of prostaglandin and nitric oxide production by the macrophage. The possible role of parasite components in the impaired accessory cell function of PECs was investigated and hemozoin, the end-product of the hemoglobin catabolism by intraerythrocytic malaria parasites, was found to induce similar infection-associated deficiencies in vitro. Moreover, hemozoin, was shown to mimic the immunosuppressive effects induced in PECs during in-vivo infections with P. chabaudi. In conclusion, we propose that hemozoin is a key factor in the malaria-associated immunosuppression, affecting both the antigen processing and immunomodulatory functions of macrophages.
Scorza
T
T
Department of Immunology, Parasitology and Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnology, Vrije Universiteit Brussel, Paardenstraat 65, 1640 Sint Genesius Rode, Belgium.
Magez
S
S
Brys
L
L
De Baetselier
P
P
D000208:Acute Disease; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006420:Hemeproteins / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D006825:Hybridomas / Q000378:metabolism; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D018512:Parasitemia / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000737:chemistry*; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D006420:Hemeproteins; D007376:Interleukin-2; D011453:Prostaglandins; D009569:Nitric Oxide; C020753:hemozoin