NK cell activation and protection occur independently of natural killer T cells during Trypanosoma cruzi infection

Abstract
Natural killer T (NKT) cells regulate aspects of pro-inflammatory and anti-inflammatory responses and contribute to the control of infections and chronic inflammatory diseases. During Trypanosoma cruzi infection both NKT cells and NK cells are critical to the protective response. How NKT cells interact and possibly regulate NK cells during infections remains uncertain. In vivo studies have demonstrated that specific activation of NKT cells with α-galactosylceramide (α-GalCer) leads to NK cell activation. These results suggest that during some infections activated NKT cells might regulate NK cell activation and functions. Therefore, using gene-deficient mice that lack NKT cells and antibody-treated mice that lack NK cells, we investigated the interactions of NKT cells and NK cells during experimental T. cruzi infection. We report here that during acute T. cruzi infection spleen and liver NK cell activation and cytolytic activity occur independently of NKT cells. Moreover, NK cell protection occurs independently of NKT cells. In contrast to these results that fail to demonstrate an interdependence, at day 4 of infection the number of liver NK cells is controlled by NKT cells. Thus, during T. cruzi infection, regulation of the number of liver NK cells requires NKT cells, but the activation of NK cells and protection by NK cells does not. The data presented here argue that during infections NK cell activation and protection occur independently of NKT cells.