Internal Indigestion

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Science  24 Apr 2009:
Vol. 324, Issue 5926, pp. 440
DOI: 10.1126/science.324_440a

T cell—mediated responses to extracellular pathogens are initiated through a process called cross-presentation: Pathogens are internalized by dendritic cells via phagocytosis, partially degraded, and then presented on the cell surface by class I major histocompatibility molecules for recognition by cytotoxic T cells. Several immune cell types possess phagocytic capacity; in most cases, however, this leads to pathogen degradation. In contrast, dendritic cells that express CD8 are able to cross-present because of the low proteolytic activity and slightly alkaline pH of their phagosomes.

Savina et al. demonstrate that in contrast to non—cross-presenting dendritic cell subsets, CD8+ dendritic cells assemble the NADPH oxidase complex (NOX2) in their phagosomal membranes, which results in reactive oxygen species production and the maintenance of a high pH. Proper localization of a NOX2 subunit to the phagosome was dependent on the small GTPase Rac2. In the absence of Rac2, NOX2 did not assemble, high phagosomal pH was not maintained, and consequently, CD8+ dendritic cells were not active in cross-presentation. These data provide a molecular rationale for why only particular subsets of phagocytes can trigger cytotoxic T cell responses to extracellular infections.

Immunity 30, 10.1016/j.immuni.2009.01.013 (2009).

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