Activation Pathways of Murine Macrophages by Lipophosphoglycan from Strains of Leishmania major (FV1 and LV39).

Autor: Mançur Santos V; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296-710, Brasil.; Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BA 40.026-010, Brasil., Goicochea AMC; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296-710, Brasil.; Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BA 40.026-010, Brasil., Soares Neto AJ; Núcleo de Agentes Infecciosos e Vetores (NAIVE), Universidade Federal do Oeste da Bahia (UFOB), Barreiras, BA 47808-021, Brasil., Jesus Santos FH; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296-710, Brasil.; Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BA 40.026-010, Brasil., Lobo da Silva J; Laboratório de Medicina e Saúde Pública de Precisão (MeSP2), Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA 40296-710, Brazil., Araújo-Santos T; Núcleo de Agentes Infecciosos e Vetores (NAIVE), Universidade Federal do Oeste da Bahia (UFOB), Barreiras, BA 47808-021, Brasil., Paiva Farias L; Laboratório de Medicina e Saúde Pública de Precisão (MeSP2), Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA 40296-710, Brazil., Brodskyn CI; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296-710, Brasil.; Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BA 40.026-010, Brasil., M Borges V; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296-710, Brasil.; Faculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BA 40.026-010, Brasil., Pedro Soares R; Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, MG 30.190-009, Brasil., Berlink Lima J; Núcleo de Agentes Infecciosos e Vetores (NAIVE), Universidade Federal do Oeste da Bahia (UFOB), Barreiras, BA 47808-021, Brasil.
Jazyk: angličtina
Zdroj: ACS infectious diseases [ACS Infect Dis] 2024 Sep 23. Date of Electronic Publication: 2024 Sep 23.
DOI: 10.1021/acsinfecdis.4c00295
Abstrakt: Lipophosphoglycan (LPG) is an important Leishmania virulence factor. It is the most abundant surface glycoconjugate in promastigotes, playing an important role in the interaction with phagocytic cells. While LPG is known to modulate the macrophage immune response during infection, the activation mechanisms triggered by this glycoconjugate have not been fully elucidated. This work investigated the role that LPGs purified from two strains of Leishmania major (FV1 and LV39) play in macrophage activation, considering the differences in their biochemical structures. Bone marrow-derived macrophages from BALB/c mice were stimulated with 10 μg/mL purified LPG from the LV39 and FV1 strains. We then measured the production of nitric oxide (NO) and cytokines, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the activation of MAPK pathways. LPG from the LV39 strain, which has longer poly-galactosylated side chains, induced a more pro-inflammatory profile than that from the FV1 strain. This included higher production of NO, TNF-α, and PGE2, and increased expression of COX-2 and iNOS. Additionally, the phosphorylation of ERK-1/2 and JNK was elevated in macrophages exposed to LPG from the LV39 strain. No difference in IL-10 production was observed in cells stimulated by both LPG. Thus, intraspecific structural differences in LPG contribute to distinct innate immune responses in macrophages.
Databáze: MEDLINE