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

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 monocytogenes infection 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. monocytogenes infection. 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. monocytogenes infection, 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.