Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis

作者：Stanley Amanda C^*; Zhou Yonghong; Amante Fiona H; Randall Louise M; Haque Ashraful; Pellicci Daniel G; Hill Geoff R; Smyth Mark J; Godfrey Dale I; Engwerda Christian R

来源：PLoS Pathogens, 2008, 4(2): e1000028.

DOI：10.1371/journal.ppat.1000028

We report that natural killer T (NKT) cells play only a minor physiological role in protection from Leishmania donovani infection in C57BL/6 mice. Furthermore, attempts at therapeutic activation of invariant NKT (iNKT) cells with alpha-galactosylceramide (alpha-GalCer) during L. donovani infection exacerbated, rather than ameliorated, experimental visceral leishmaniasis. The inability of alpha-GalCer to promote anti-parasitic immunity did not result from inefficient antigen presentation caused by infection because alpha-GalCer-loaded bone marrow-derived dendritic cells were also unable to improve disease resolution. The immune-dampening affect of alpha-GalCer correlated with a bias towards increased IL-4 production by iNKT cells following alpha-GalCer stimulation in infected mice compared to naive controls. However, studies in IL-4-deficient mice, and IL-4 neutralisation in cytokine-sufficient mice revealed that alpha-GalCer-induced IL-4 production during infection had only a minor role in impaired parasite control. Analysis of liver cell composition following alpha-GalCer stimulation during an established L. donovani infection revealed important differences, predominantly a decrease in IFN gamma(+) CD8(+) T cells, compared with control-treated mice. Our data clearly illustrate the double-edged sword of NKT cell-based therapy, showing that in some circumstances, such as when sub-clinical or chronic infections exist, iNKT cell activation can have adverse outcomes.

• 出版日期2008-2
• 单位河北医科大学