title: Histoplasma capsulatum cell wall {beta}-glucan induces lipid body formation through CD18, TLR2, and dectin-1 receptors: correlation with leukotriene B4 generation and role in HIV-1 infection.
abstract: Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B(4) plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B(4) and PGE(2). Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly beta-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that beta-glucan plays a signaling role in LB formation. In agreement with this hypothesis, beta-glucan-elicited LB formation was inhibited in leukocytes from 5-LO(-/-), CD18(low) and TLR2(-/-) mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after beta-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Carlos Artério
authors.initials: CA
authors.lastname: Sorgi
authors.forename: Adriana
authors.initials: A
authors.lastname: Secatto
authors.forename: Caroline
authors.initials: C
authors.lastname: Fontanari
authors.forename: Walter Miguel
authors.initials: WM
authors.lastname: Turato
authors.forename: Caroline
authors.initials: C
authors.lastname: Belangér
authors.forename: Alexandra Ivo
authors.initials: AI
authors.lastname: de Medeiros
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marleau
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Patrícia Torres
authors.initials: PT
authors.lastname: Bozza
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000328:Adult; D000818:Animals; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology; D008055:Lipids; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D015388:Organelles / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D047071:beta-Glucans / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D018821:CD18 Antigens; D037181:Lectins, C-Type; D007975:Leukotriene B4; D008055:Lipids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051195:Toll-Like Receptor 2; D047071:beta-Glucans; D000099181:Dectin-1