Splenic differentiation and emergence of CCR5<sup>+</sup>CXCL9<sup>+</sup>CXCL10<sup>+</sup> monocyte-derived dendritic cells in the brain during cerebral malaria.

Hirako, Isabella C; Ataide, Marco A; Faustino, Lucas; Assis, Patricia A; Sorensen, Elizabeth W; Ueta, Hisashi; Araújo, Natalia M; Menezes, Gustavo B et al. · Nat Commun · 2016

basic_science · Level V

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Abstract

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b<sup>+</sup>F4/80<sup>+</sup>CD11c<sup>+</sup>MHCII<sup>high</sup>DC-SIGN<sup>high</sup>Ly6c<sup>+</sup> and express high levels of CCR5, CXCL9 and CXCL10 (CCR5<sup>+</sup>CXCL9/10<sup>+</sup> MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5<sup>+</sup>CXCL9/10<sup>+</sup> MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8<sup>+</sup> T lymphocytes, leading to a lethal neuropathological syndrome.

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