Characterization of Early Gamma Interferon (IFN-γ) Expression during Murine Listeriosis: Identification of NK1.1+CD11c+Cells as the Primary IFN-γ-Expressing Cells

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Abstract
Though it is well established that gamma interferon (IFN-γ) is crucial to the early innate defense of murine listeriosis, its sources remain controversial. In this study, intracellular cytokine staining of IFN-γ-expressing splenocytes early afterListeria monocytogenesinfection revealed that NK1.1+, CD11c+, CD8+T, and CD4+T cells expressed IFN-γ 24 h after infection. Contrary to the previous report, most IFN-γ+dendritic cells (DC) were CD8α−DC. Unexpectedly, almost all CD11c+IFN-γ-expressing cells also expressed NK1.1. These NK1.1+CD11c+cells represented primary IFN-γ-expressing cells after infection. In situ studies showed these NK1.1+CD11c+cells were recruited to the borders of infectious foci and expressed IFN-γ. A significant NK1.1+CD11c+population was found in uninfected spleen, lymph node, blood, and bone marrow cells. And its number increased significantly in spleen, lymph node, and bone marrow afterL. monocytogenesinfection. Using interleukin-12 (IL-12) p40−/−mice, IFN-γ expression was found to be largely IL-12 p40 dependent, and the number of IFN-γ-expressing cells was only about one-third of that of wild-type mice. Moreover, the IFN-γ expression was absolutely dependent on liveL. monocytogenesinfection, as no IFN-γ was detected after inoculation of heat-killedL. monocytogenes. Our findings not only provide an insight into IFN-γ expression after in vivo infection but may also change the current perceptions of DC and natural killer cells.