title: Paracoccidioides brasiliensis lipids modulate macrophage activity via Toll-dependent or independent mechanisms.
abstract: The macrophages are the first host cells that interact with the fungus Paracoccidioides brasiliensis, but the main mechanisms that regulate this interaction are not well understood. Because the role played by P. brasiliensis lipids in macrophage activation was not previously investigated, we aimed to assess the influence of diverse lipid fractions from P. brasiliensis yeasts in this process. The possible participation of TLR2 and TLR4 signaling was also evaluated using TLR2- and TLR4-defective macrophages. Four lipid-rich fractions were studied as follows: F1, composed by membrane phospholipids and neutral lipids, F2 by glycolipids of short chain, F3a by membrane glycoproteins anchored by glycosylphosphatidylinositol (GPI) groups, and F3b by glycolipids of long chain. All assayed lipid fractions were able to activate peritoneal macrophages and induce nitric oxide (NO) production. Importantly, the F1 and F3a fractions exerted opposite effects in the control of P. brasiliensis uptake and killing, but both fractions inhibited cytokines production. Furthermore, the increased NO production and expression of costimulatory molecules induced by F3a was shown to be TLR2 dependent although F1 used Toll-independent mechanisms. In conclusion, our work suggests that lipid components may play a role in the innate immunity against P. brasiliensis infection using Toll-dependent and independent mechanisms to control macrophage activation.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Flávio V
authors.initials: FV
authors.lastname: Loures
authors.forename: Heleni
authors.initials: H
authors.lastname: Stroeder
authors.forename: Igor
authors.initials: I
authors.lastname: Almeida
authors.forename: Vera L G
authors.initials: VL
authors.lastname: Calich
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D008055:Lipids / Q000276:immunology* / Q000302:isolation & purification; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D009569:Nitric Oxide / Q000378:metabolism; D010228:Paracoccidioides / Q000737:chemistry / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D016207:Cytokines; D008055:Lipids; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide