title: Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection.
abstract: The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in sugars that branch off the conserved Gal(β1,4)Man(α1)-PO4 backbone of repeat units. Here, the immunomodulatory activity of LPGs from Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis, was evaluated in two strains from Brazil. One strain (PH8) was originally isolated from the sand fly and the other (Josefa) was isolated from a human case. The ability of purified LPGs from both strains was investigated during in vitro interaction with peritoneal murine macrophages and CHO cells and in vivo infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-κB inhibitor p-IκBα, but were not able to translocate NF-κB. In vivo experiments with sand flies showed that both stains were able to sustain infection in L. migonei. A preliminary biochemical analysis indicates intraspecies variation in the LPG sugar moieties. However, they did not result in different activation profiles of the innate immune system. Also those polymorphisms did not affect infectivity to the sand fly.
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.|Departamento de Parasitologia, UFMG, Belo Horizonte, Minas Gerais, Brazil.
authors: Paula M
authors: PM
authors: Nogueira
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Rafael R
authors: RR
authors: Assis
authors: Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Departamento de Ciências Biológicas, UNIFESP, São Paulo, São Paulo, Brazil.
authors: Ana C
authors: AC
authors: Torrecilhas
authors: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, UFRJ, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Elvira M
authors: EM
authors: Saraiva
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Natália L
authors: NL
authors: Pessoa
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Marco A
authors: MA
authors: Campos
authors: Centro de Pesquisas Leônidas e Maria Deane/FIOCRUZ, Manaus, Amazonas, Brazil.
authors: Eric F
authors: EF
authors: Marialva
authors: Centro de Pesquisas Leônidas e Maria Deane/FIOCRUZ, Manaus, Amazonas, Brazil.
authors: Cláudia M
authors: CM
authors: Ríos-Velasquez
authors: Centro de Pesquisas Leônidas e Maria Deane/FIOCRUZ, Manaus, Amazonas, Brazil.
authors: Felipe A
authors: FA
authors: Pessoa
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Nágila F
authors: NF
authors: Secundino
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Jerônimo N
authors: JN
authors: Rugani
authors: Laboratório de Parasitologia Experimental, Departamento de Biologia, Universidad de Los Andes, Mérida, Venezuela.
authors: Elsa
authors: E
authors: Nieves
authors: Department of Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky, United States of America.
authors: Salvatore J
authors: SJ
authors: Turco
authors: Departamento de Parasitologia, UFMG, Belo Horizonte, Minas Gerais, Brazil.
authors: Maria N
authors: MN
authors: Melo
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Rodrigo P
authors: 0000-0002-7966-3629
authors: RP
authors: Soares
mesh_terms: D000818:Animals; D001938:Brazil; D016466:CHO Cells; D003412:Cricetulus; D016207:Cytokines / Q000276:immunology; D006028:Glycosphingolipids / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007894:Leishmania mexicana / Q000737:chemistry*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects; D011576:Psychodidae / Q000469:parasitology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D006028:Glycosphingolipids; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C008290:lipophosphonoglycan; D020929:Mitogen-Activated Protein Kinase Kinases