title: MyD88-dependent activation of dendritic cells and CD4(+) T lymphocytes mediates symptoms, but is not required for the immunological control of parasites during rodent malaria.
abstract: We investigated the role of different TLRs and MyD88 in host resistance to infection and malaria pathogenesis. TLR2(-/-), TLR4(-/-), TLR6(-/-), TLR9(-/-) or CD14(-/-) mice showed no change in phenotypes (parasitemia, body weight and temperature) when infected with Plasmodium chabaudi chabaudi (AS). MyD88(-/-) mice displayed comparable ability to wild type animals in controlling and clearing parasitemia. Importantly, MyD88(-/-) mice exhibited impaired production of TNF-alpha and IFN-gamma as well as attenuated symptoms, as indicated by changes in body weight and temperature during parasitemia. Consistently, CD11b(+) monocytes and CD11c(+) dendritic cells from infected MyD88(-/-) mice were shown impaired for production of pro-inflammatory cytokines, and in initiating CD4(+) T cell responses. Importantly, the inhibition of T cell activation with anti-CD134L, mostly inhibited IFN-gamma, partially inhibited TNF-alpha production, and protected the animals from malaria symptoms. Our findings suggest that MyD88 and possibly its associated TLRs expressed by dendritic cells play an important role in pro-inflammatory responses, T cell activation, and pathogenesis of malaria, but are not critical for the immunological control of the erythrocytic stage of P. chabaudi.
authors.affiliation: Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors.forename: Bernardo S
authors.initials: BS
authors.lastname: Franklin
authors.forename: Soraia O
authors.initials: SO
authors.lastname: Rodrigues
authors.forename: Lis R
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Roberta V
authors.initials: RV
authors.lastname: Oliveira
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Goncalves
authors.forename: Policarpo A
authors.initials: PA
authors.lastname: Sales-Junior
authors.forename: Eneida P
authors.initials: EP
authors.lastname: Valente
authors.forename: Jacqueline I
authors.initials: JI
authors.lastname: Alvarez-Leite
authors.forename: Catherine
authors.initials: C
authors.lastname: Ropert
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D018512:Parasitemia / Q000276:immunology; D016788:Plasmodium chabaudi / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors