alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria.

Gonzalez-Aseguinolaza G, de Oliveira C, Tomaska M, Hong S, Bruna-Romero O, Nakayama T, Taniguchi M, Bendelac A, Van Kaer L, Koezuka Y, Tsuji M
Proc Natl Acad Sci U S A. 2000 97 (15): 8461-6

PMID: 10900007 · PMCID: PMC26970 · DOI:10.1073/pnas.97.15.8461

Natural killer T (NKT) cells are a unique population of lymphocytes that coexpress a semiinvariant T cell and natural killer cell receptors, which are particularly abundant in the liver. To investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid, alpha-galactosylceramide (alpha-GalCer), known to selectively activate Valpha14 NKT cells in the context of CD1d molecules, was administered to sporozoite-inoculated mice. The administration of alpha-GalCer resulted in rapid, strong antimalaria activity, inhibiting the development of the intrahepatocytic stages of the rodent malaria parasites Plasmodium yoelii and Plasmodium berghei. The antimalaria activity mediated by alpha-GalCer is stage-specific, since the course of blood-stage-induced infection was not inhibited by administration of this glycolipid. Furthermore, it was determined that IFN-gamma is essential for the antimalaria activity mediated by the glycolipid. Taken together, our results provide the clear evidence that NKT cells can mediate protection against an intracellular microbial infection.

MeSH Terms (17)

Animals Antigens, CD1 Antimalarials Galactosylceramides Interferon-gamma Interleukin-12 Killer Cells, Natural Liver Lymphocyte Activation Malaria Mice Mice, Inbred BALB C Mice, Inbred C57BL Plasmodium berghei Plasmodium yoelii Receptors, Antigen, T-Cell, alpha-beta T-Lymphocytes

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