Splenic differentiation and emergence of CCR5+CXCL9+CXCL10+monocyte-derived dendritic cells in the brain during cerebral malaria.
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.
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte MG 30190-002, Brazil.|Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
Isabella C
IC
Hirako
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte MG 30190-002, Brazil.|Departamento de Bioquímica e Imunologia and Centro de Biologia Gastrointestinal, Departamento de Morfologia, Universidade Federal of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte MG 31270-901, Brazil.
Marco A
MA
Ataide
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
Lucas
L
Faustino
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte MG 30190-002, Brazil.
Patricia A
PA
Assis
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
Elizabeth W
EW
Sorensen
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
Hisashi
0000-0003-2237-2262
H
Ueta
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte MG 30190-002, Brazil.|Departamento de Bioquímica e Imunologia and Centro de Biologia Gastrointestinal, Departamento de Morfologia, Universidade Federal of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte MG 31270-901, Brazil.
Natalia M
NM
Araújo
Departamento de Bioquímica e Imunologia and Centro de Biologia Gastrointestinal, Departamento de Morfologia, Universidade Federal of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte MG 31270-901, Brazil.
Gustavo B
GB
Menezes
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
Andrew D
0000-0001-9679-7912
AD
Luster
Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte MG 30190-002, Brazil.|Departamento de Bioquímica e Imunologia and Centro de Biologia Gastrointestinal, Departamento de Morfologia, Universidade Federal of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte MG 31270-901, Brazil.|Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01655, USA.
Ricardo T
RT
Gazzinelli
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D054357:Chemokine CXCL10 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D010962:Plasmodium berghei / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000502:physiology*
D000953:Antigens, Protozoan; C000592874:CCR5 protein, mouse; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D019713:Receptors, CCR5