Cutting edge: Clec9A+ dendritic cells mediate the development of experimental cerebral malaria.
Plasmodium infections trigger strong innate and acquired immune responses, which can lead to severe complications, including the most feared and often fatal cerebral malaria (CM). To begin to dissect the roles of different dendritic cell (DC) subsets in Plasmodium-induced pathology, we have generated a transgenic strain, Clec9A-diphtheria toxin receptor that allows us to ablate in vivo Clec9A(+) DCs. Specifically, we have analyzed the in vivo contribution of this DC subset in an experimental CM model using Plasmodium berghei, and we provide strong evidence that the absence of this DC subset resulted in complete resistance to experimental CM. This was accompanied with dramatic reduction of brain CD8(+) T cells, and those few cerebral CD8(+) T cells present had a less activated phenotype, unlike their wildtype counterparts that expressed IFN-γ and especially granzyme B. This almost complete absence of local cellular responses was also associated with reduced parasite load in the brain.
School of Biological Sciences, Nanyang Technological University, Singapore 637551.
Lucia
L
Piva
Piotr
P
Tetlak
Carla
C
Claser
Klaus
K
Karjalainen
Laurent
L
Renia
Christiane
C
Ruedl
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D016923:Cell Death / Q000276:immunology; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000502:physiology*; D016779:Malaria, Cerebral / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*
D039521:CD11c Antigen; C529914:Clec9a protein, mouse; D004167:Diphtheria Toxin; D037181:Lectins, C-Type; D011971:Receptors, Immunologic