Critical proinflammatory and anti-inflammatory functions of different subsets of CD1d-restricted natural killer T cells during Trypanosoma cruzi infection.
Trypanosoma cruzi infects 15 to 20 million people in Latin America and causes Chagas disease, a chronic inflammatory disease with fatal cardiac and gastrointestinal sequelae. How the immune response causes Chagas disease is not clear, but during the persistent infection both proinflammatory and anti-inflammatory responses are critical. Natural killer T (NKT) cells have been shown to regulate immune responses during infections and autoimmune diseases. We report here that during acute T. cruzi infection NKT-cell subsets provide distinct functions. CD1d(-/-) mice, which lack both invariant NKT (iNKT) cells and variant NKT (vNKT) cells, develop a mild phenotype displaying an increase in spleen and liver mononuclear cells, anti-T. cruzi antibody response, and muscle inflammation. In contrast, Jalpha18(-/-) mice, which lack iNKT cells but have vNKT cells, develop a robust phenotype involving prominent spleen, liver, and skeletal muscle inflammatory infiltrates comprised of NK, dendritic, B and T cells. The inflammatory cells display activation markers; produce more gamma interferon, tumor necrosis factor alpha, and nitric oxide; and show a diminished antibody response. Strikingly, most Jalpha18(-/-) mice die. Thus, in response to the same infection, vNKT cells appear to augment a robust proinflammatory response, whereas the iNKT cells dampen this response, possibly by regulating vNKT cells.
Duthie
Malcolm S
MS
IDRI, 1124 Columbia St., Ste. 600, Seattle, WA 98104, USA.
Kahn
Maria
M
White
Maria
M
Kapur
Raj P
RP
Kahn
Stuart J
SJ
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018949:Antigens, CD1 / Q000502:physiology*; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D014355:Chagas Disease / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000276:immunology; D009220:Myositis / Q000209:etiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000913:Antibodies, Protozoan; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain; D009569:Nitric Oxide; D007371:Interferon-gamma