title: Cutting edge: the acquisition of TLR tolerance during malaria infection impacts T cell activation.
abstract: An effective immune response to infection requires control of pathogen growth while minimizing inflammation-associated pathology. During malaria infection, this balance is particularly important. Murine malaria is characterized by early production of proinflammatory cytokines, which declines in the face of continuing parasitemia. The mechanism by which this occurs remains poorly understood. In this study, we investigated the role of dendritic cells (DCs) in regulating pro- and anti-inflammatory cytokine responses. As malaria infection progresses, DCs become refractory to TLR-mediated IL-12 and TNF-alpha production, while increasing their ability to produce IL-10 and retaining the capacity for activation of naive T cells. IL-12-secreting DCs from early infection stimulate an IFN-gamma-dominated T cell response, whereas IL-10-secreting DCs from later stages induce an IL-10-dominated T cell response. We suggest that phenotypic changes in DCs during Plasmodium yoelii infection represent a mechanism of controlling host inflammation while maintaining effective adaptive immunity.
authors.affiliation: Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Perry
authors.forename: Christine S
authors.initials: CS
authors.lastname: Olver
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burnett
authors.forename: Anne C
authors.initials: AC
authors.lastname: Avery
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004731:Endotoxins / Q000008:administration & dosage / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051193:Toll-Like Receptors
chemical_list: D016207:Cytokines; D004731:Endotoxins; D018984:Epitopes, T-Lymphocyte; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D020066:Merozoite Surface Protein 1; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D016753:Interleukin-10; D007371:Interferon-gamma