Coordinating innate immune cells to optimize microbial killing

Abstract

The mechanisms underlying innate immune cell trafficking and activation during infection remain incompletely defined. In this issue of Immunity, Kang et al. (2008) begin to reveal the cytokine and chemokine cascades that coordinate cellular responses induced by microbial pathogens.

Figure 1. Sequential Activation of Innate Immune Responses during Bacterial Infection

After systemic administration of L. monocytogenes, dendritic cells (DCs) transport bacteria to the white-pulp areas of the spleen, where they initiate secretion of chemokines required for recruitment of natural killer (NK) cells and monocytes (left). DCs undergo MyD88-dependent activation and secrete IL-12 and IL-18 that in turn activate newly recruited NK cells to produce IFN-γ. Recruited cells are organized in clusters; monocytes are positioned in proximity to infected cells, and NK cells form a cuff at the periphery (middle). NK-derived IFN-γ induces monocyte activation. Monocyte activation leads to upregulation of MHC class II and iNOS expression and subsequent differentiation into TipDCs. TipDCs sense microbial infection in a MyD88-dependent manner and secrete TNF-α and nitric oxide (NO), ultimately leading to restriction of bacterial replication (right).