title: Toll-Like Receptor 2 Is Required for Inflammatory Process Development duringLeishmania infantumInfection.
abstract: Visceral leishmaniasis (VL) is a chronic and fatal disease caused byLeishmania infantumin Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Among inflammatory cells, neutrophils are recruited to the site ofLeishmaniainfection, and these cells may control parasite replication through oxidative or non-oxidative mechanisms. The recruitment, activation and functions of the neutrophils are coordinated by pro-inflammatory cytokines and chemokines during recognition of the parasite by pattern recognition receptors (PRRs). Here, we demonstrated that the Toll-like receptor 2 (TLR2) signaling pathway contributes to the development of the innate immune response duringL. infantuminfection. The protective mechanism is related to the appropriate recruitment of neutrophils to the inflammatory site. Neutrophil migration is coordinated by DCs that produce CXCL1 and provide a prototypal Th1 and Th17 environment when activated via TLR2. Furthermore, infected TLR2-/-mice failed to inducenitric oxide synthase(iNOS) expression in neutrophils but not in macrophages.In vitro, infected TLR2-/-neutrophils presented deficient iNOS expression, nitric oxide (NO) and TNF-α production, decreased expression of CD11b and reducedL. infantumuptake capacity. The non-responsive state of neutrophils is associated with increased amounts of IL-10. Taken together, these data clarify new mechanisms by which TLR2 functions in promoting the development of the adaptive immune response and effector mechanisms of neutrophils duringL. infantuminfection.
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Laís A
authors.initials: LA
authors.lastname: Sacramento
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Jéssica L
authors.initials: JL
authors.lastname: da Costa
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Mikhael H F
authors.initials: MH
authors.lastname: de Lima
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Sampaio
authors.affiliation: Center for Biology and Health Sciences, Federal University of Sergipe Aracaju, Brazil.
authors.forename: Roque P
authors.initials: RP
authors.lastname: Almeida
authors.affiliation: Department of Biochemistry and Immunology, University of São PauloRibeirão Preto, Brazil; Department of Pharmacology, Ribeirão Preto Medical School, University of São PauloRibeirão Preto, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo Ribeirão Preto, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Carregaro
keywords: Leishmania infantum; TLR2; dendritic cell maturation; neutrophil activation; visceral leishmaniasis