MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major.
Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)-dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II-positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II-negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNgamma. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8alpha+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Maria P
MP
Lemos
Fatima
F
Esquivel
Phillip
P
Scott
Terri M
TM
Laufer
D000818:Animals; D017951:Antigen Presentation; D039481:CD11b Antigen / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
D039481:CD11b Antigen; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II