TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection.
Dendritic cells (DCs) present microbial antigens to T cells and provide inflammatory signals that modulate T cell differentiation. While the role of DCs in adaptive immunity is well established, their involvement in innate immune defenses is less well defined. We have identified a TNF/iNOS-producing (Tip)-DC subset in spleens of Listeria monocytogenes-infected mice that is absent from CCR2-deficient mice. The absence of Tip-DCs results in profound TNF and iNOS deficiencies and an inability to clear primary bacterial infection. CD8 and CD4 T cell responses to L. monocytogenes antigens are preserved in CCR2-deficient mice, indicating that Tip-DCs are not essential for T cell priming. Tip-DCs, as the predominant source of TNF and iNOS during L. monocytogenes infection, orchestrate and mediate innate immune defense against this intracellular bacterial pathogen.
Serbina
Natalya V
NV
Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Immunology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Salazar-Mather
Thais P
TP
Biron
Christine A
CA
Kuziel
William A
WA
Pamer
Eric G
EG
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D007113:Immunity, Innate; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000943:Antigens, Differentiation; D039481:CD11b Antigen; D039521:CD11c Antigen; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse