RESUMO

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+F4/80+CD11c+MHCIIhighDC-SIGNhighLy6c+ and express high levels of CCR5, CXCL9 and CXCL10 (CCR5+CXCL9/10+ MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5+CXCL9/10+ MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8+ T lymphocytes, leading to a lethal neuropathological syndrome.

Assuntos

Encéfalo/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/fisiologia , Malária Cerebral/imunologia , Baço/fisiologia , Animais , Antígenos de Protozoários/imunologia , Encéfalo/citologia , Encéfalo/patologia , Diferenciação Celular/imunologia , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/metabolismo , Modelos Animais de Doenças , Humanos , Malária Cerebral/parasitologia , Malária Cerebral/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/citologia , Plasmodium berghei/imunologia , Receptores CCR5/metabolismo , Baço/citologia