Leukotrienes Are Potent Adjuvant during Fungal Infection: Effects on Memory T Cells

Autor(es)

Medeiros, Alexandra I. ^[1] ; Sa-Nunes, Anderson ^[1] ; Turato, Walter M. ^[1] ; Secatto, Adriana ^[1] ; Frantz, Fabiani G. ^[1] ; Sorgi, Carlos A. ^[1] ; Serezani, Carlos H. ^[2] ; Deepe, Jr., George S. ^[3] ; Faccioli, Lucia H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bramatol, BR-14040903 Sao Paulo - Brazil

^[2] Univ Michigan Hlth Syst, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 - USA

^[3] Univ Cincinnati, Vet Affairs Hosp, Div Infect Dis, Coll Med, Cincinnati, OH 45267 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY; v. 181, n. 12, p. 8544-8551, Dec. 2008.
• Área do conhecimento: Ciências Biológicas - Imunologia
• Citações Web of Science: 34
• Assunto(s): Vacinas fúngicas Antígenos de fungos Leucotrienos

Resumo

Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB4 induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB4 is also important in early effector T cell recruitment that is mediated by LTB4 receptor 1, the high-affinity receptor for LTB4. The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB4 and IFN- production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase-/-, a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-BETA as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase-/--infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis. (AU)

• Processo FAPESP: 02/07849-7 - Estudo sobre o papel imunomodulatório de leucotrienos na proteção induzida por exoantígenos de "Histoplasma capsulatum"
• Beneficiário: Alexandra Ivo de Medeiros
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• 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