The receptor Slamf1 on the surface of myeloid lineage cells controls susceptibility to infection by Trypanosoma cruzi.
Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1-/- mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1-/- mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection.
Centro de Biología Molecular "Severo Ochoa"-CSIC-UAM, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Jossela
J
Calderón
Elena
E
Maganto-Garcia
Carmen
C
Punzón
Javier
J
Carrión
Cox
C
Terhorst
Manuel
M
Fresno
D000818:Animals; D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000469:parasitology*; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D006321:Heart / Q000469:parasitology; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000469:parasitology; D009206:Myocardium / Q000378:metabolism; D018512:Parasitemia; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014349:Trypanosoma cruzi / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D015703:Antigens, CD; D016207:Cytokines; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C000604062:Slamf1 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma