Abstract

Abstract NK cells and CD8+ T cells play vital roles in containing and eliminating systemic cytomegalovirus. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Notably, naïve salivary gland NK cells have a reduced expression of CD27, are nearly absent of the inhibitory receptor KLRG1, yet are mostly CD11b positive. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer (LTi) NK-like cells and are not thymic derived. During the course of MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited effector functions in vivo. Salivary gland NK cell effector functions are not regulated by iNKT or Treg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that latency in SMG may result from both the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

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