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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Histoplasma capsulatum Cell Wall beta-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B-4 Generation and Role in HIV-1 Infection

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Sorgi, Carlos Arterio [1] ; Secatto, Adriana [1] ; Fontanari, Caroline [1] ; Turato, Walter Miguel [1] ; Belanger, Caroline [2] ; de Medeiros, Alexandra Ivo [1] ; Kashima, Simone [3] ; Marleau, Sylvie [2] ; Covas, Dimas Tadeu [4] ; Bozza, Patricia Torres [5] ; Faccioli, Lucia Helena [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Sao Paulo - Brazil
[2] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7 - Canada
[3] Univ Sao Paulo, Fundacao Hemoctr Ribeirao Preto, Sao Paulo - Brazil
[4] Univ Sao Paulo, Dept Clin Med, Fac Med Ribeirao Preto, Sao Paulo - Brazil
[5] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF IMMUNOLOGY; v. 182, n. 7, p. 4025-4035, Apr. 2009.
Área do conhecimento: Ciências Biológicas - Imunologia
Citações Web of Science: 37
Assunto(s):Proteínas do tecido nervoso   Vírus de RNA   HIV-1   Técnicas imunoenzimáticas   ELISA   Leucotrienos

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 B4 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 B4 and PGE2. 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-/-, CD18low 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. (AU)

Processo FAPESP: 02/12856-2 - Modulação das respostas imunes inata e adquirida por leucotrienos e prostaglandinas
Beneficiário:Lúcia Helena Faccioli
Linha de fomento: Auxílio à Pesquisa - Temático