title: Supplementation of CXCL12 (CXCL12) induces homing of CD11c+ dendritic cells to the spleen and enhances control of Plasmodium berghei malaria in BALB/c mice.
abstract: In malaria, parasitaemia is controlled in the spleen, a multicomponent organ that undergoes changes in its cellular constituents to control the parasite. During this process, dendritic cells (DCs) orchestrate the positioning of effector cells in a timely manner for optimal parasite clearance. We have recently demonstrated that CXCL12 [stromal cell-derived factor-1 (CXCL12)] supplementation partially restores the ability to control parasitaemia in Plasmodium berghei-infected mice. In the present study, we investigated the nature of the DCs involved by flow cytometry and immunohistochemistry of CD11c(+) cells. Flow cytometry of bone marrow cells showed that infection with P. berghei did not alter the proportion of CD11c(+) cells present in this haematopoietic compartment, while CXCL12 supplementation of naïve uninfected mice induced only minor increases in the population of CD11c(+) cells. In the spleen, P. berghei infection alone resulted in an increase in CD11c(+) cells as compared with naïve animals. Exogenously administered CXCL12 in the absence of infection resulted in a significant expansion of the splenic CD11c(+) population, and this effect was even more pronounced in infected and supplemented mice. Immunohistochemistry revealed that CD11c(+) cells infiltrated the perivascular areas and marginal zone of the spleen in infected animals treated with CXCL12, suggesting that this chemokine induces homing of CD11c(+) dendritic cells to the splenic compartment. Our results show that small amounts of CXCL12 supplementation are effective in recruiting DCs to the spleens of both uninfected and infected mice, suggesting the participation of CXCL12 and CD11c(+) cells in the establishment of an adequate environment in the spleen for malaria control.
authors.affiliation: Laboratory of Protozoology, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Margoth Ramos
authors.initials: MR
authors.lastname: Garnica
authors.forename: Luciana Vieira
authors.initials: LV
authors.lastname: de Moraes
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse