NK Cells Are Critical for Optimal Immunity to ExperimentalInfection.

Abstract

NK cells are key innate immune cells that play critical roles in host defense. Although NK cells have been shown to regulate immunity to some infectious diseases, their role in immunity tohas not been investigated. NK cells are vital sources of IFN-γ and TNF-α; two key cytokines that are known to play important roles in resistance to African trypanosomes. In this article, we show that infection withleads to increased levels of activated and functional NK cells in multiple tissue compartments. Systemic depletion of NK cells with anti-NK1.1 mAb led to increased parasitemia, which was accompanied by significant reduction in IFN-γ production by immune cells in the spleens and liver of infected mice. Strikingly, infected NFIL3mice (which genetically lack NK cell development and function) on the normally resistant background were highly susceptible toinfection. These mice developed fulminating and uncontrolled parasitemia and died significantly earlier (13 ± 1 d) than their wild-type control mice (106 ± 26 d). The enhanced susceptibility of NFIL3mice to infection was accompanied by significantly impaired cytokine (IFN-γ and TNF-α) response by CD3T cells in the spleens and liver. Adoptive transfer of NK cells into NFIL3mice before infection rescued them from acute death in a perforin-dependent manner. Collectively, these studies show that NK cells are critical for optimal resistance to, and its deficiency leads to enhanced susceptibility in infected mice.