Leishmania donovani skews the CD56+ Natural Killer T cell response during human visceral leishmaniasis

•Categorical function of CD56+ NKT cells are reported in human VL.•CD4+NKT cells are pathogenic and accumulates at infection site.•Majority of the CD56+ NKT cells are CD8+.•L. donovani prohibits CD8+CD56+ NKT cells to inter into the infection site.•CD8+NKT cells may prove protective in contact with target cells.

The objective of this study was to understand the categorical function of CD4+CD56+ and CD8+CD56+ NKT cells in human visceral leishmaniasis. These cell populations were significantly deregulated in human peripheral blood during VL. The in vitro experiments showed that CD4+NKT cells, but not CD8+NKT cells, migrated towards the Leishmania donovani infection site. Additionally, CD4+NKT cells from VL subjects primarily expressed CD25+Foxp3 and IL-10 compared with healthy subjects. However, CD8+NKT cells expressed primarily IFN-γ and killer cell immunoglobulin receptor compared with healthy subjects. Because the ratio of CD4+ and CD8+NKT cells was 1:10, adoptive transfer of CD3+CD56+ NKT cells effectively reduced the L. donovani burden in infected macrophages. This study concludes that although CD4+NKT cells are pathogenic and accumulate at the infection site, CD8+NKT cells may be protective in contact with target cells.

Graphical abstractCD4+NKT cells are pathogenic and accumulate at infection site. CD8+NKT cells, which cannot accumulate at infection site, may prove protective in contact with target cells.Figure optionsDownload full-size imageDownload as PowerPoint slide