Innate Immunity to Intracellular Bacteria

The innate immune response to intracellular bacteria is mediated mainly by phagocytes and natural killer (NK) cells. Phagocytes, initially neutrophils and later macrophages, ingest and attempt to destroy these microbes, but pathogenic intracellular bacteria are resistant to degradation within phagocytes. Products of these bacteria are recognized by TLRs and cytoplasmic proteins of the NODlike receptor (NLR) family, resulting in activation of the phagocytes (see Chapter 4). Intracellular bacteria activate NK cells by inducing expression of NK cell-activating ligands on infected cells and by stimulating dendritic cell and macrophage production of IL-12 and IL-15, both of which are NK cell-activating cytokines. The NK cells produce IFN-y, which in turn activates macrophages and promotes killing of the phagocytosed bacteria. Thus, NK cells provide an early defense against these microbes, before the development of adaptive immunity. In fact, mice with severe combined immunodeficiency, which lack T and B cells, are able to transiently control infection with the intracellular bacterium Listeria monocytogenes by NK cell-derived IFN-y production. However, innate immunity usually fails to eradicate these infections, and eradication requires adaptive cell-mediated immunity.

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