title: Innate immunomodulation to trypanosomatid parasite infections.
abstract: The recognition of invading pathogens by the innate immune system is essential for host protection against human parasites and the initiation of an effective adaptive immune response. Innate immune cells such as macrophages and dendritic cells (DCs) are involved in the first line of defense against protozoan parasites via sensing the invaders through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs). Activation of macrophages and dendritic cells starts with the interaction between microbial ligands (pathogen-associated molecular patterns - PAMPs) and PRRs, and these activated cells influence the overall immune response. Trypanosomatid PAMPs are sensed by TLRs; for example, TLR2 recognizes alkylacylglycerol and lipophosphoglycan in Trypanosoma cruzi and Leishmania, respectively; TLR2/TLR4 recognize glycoisnositolphospholipids and glycosylphosphatidyl inositol in Trypanosoma species; and TLR9 recognizes genomic DNA in Trypanosoma. TLR signaling includes the recruitment of different adaptor molecules that activate various transcription factors, such as NF-kB, IRF3/7, and MAP kinases, to induce the production of pro-inflammatory cytokines and type I interferons. Moreover, activated macrophages and dendritic cells produce ROS and NOS, which limit pathogen survival, and large amounts of cytokines; additionally, antigen presentation enhances the adaptive immune response. In this review, we highlight the recent findings on PAMP recognition in trypanosomatid infections and the signaling pathways activated by PRRs.
authors.affiliation: Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil. Electronic address: alasantos@bioqmed.ufrj.br.
authors.forename: A L A
authors.initials: AL
authors.lastname: Dos-Santos
authors.affiliation: Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Carvalho-Kelly
authors.affiliation: Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil.
authors.forename: C F
authors.initials: CF
authors.lastname: Dick
authors.affiliation: Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Meyer-Fernandes
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014352:Trypanosomiasis / Q000276:immunology*
chemical_list: D000069452:Pathogen-Associated Molecular Pattern Molecules; D051193:Toll-Like Receptors
keywords: Innate immune cells; PAMPs; TLRs; Trypanosomatid