Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis.
Interleukin (IL)-15 is a pleiotropic cytokine that regulates the proliferation and survival of many cell types. IL-15 is produced by monocytes and macrophages against infectious agents and plays a pivotal role in innate and adaptive immune responses. This study analyzed the effect of IL-15 on fungicidal activity, oxidative metabolism and cytokine production by human monocytes challenged in vitro with Paracoccidioides brasiliensis (Pb18), the agent of paracoccidioidomycosis. Peripheral blood monocytes were pre-incubated with IL-15 and then challenged with Pb18. Fungicidal activity was assessed by viable fungi recovery from cultures after plating on brain-heart infusion-agar. Superoxide anion (O₂⁻), hydrogen peroxide (H₂O₂), tumour necrosis factor-alpha (TNF-α), IL-6, IL-15 and IL-10 production by monocytes were also determined. IL-15 enhanced fungicidal activity against Pb18 in a dose-dependent pattern. This effect was abrogated by addition of anti-IL-15 monoclonal antibody. A significant stimulatory effect of IL-15 on O₂⁻ and H₂O₂ release suggests that fungicidal activity was dependent on the activation of oxidative metabolism. Pre-treatment of monocytes with IL-15 induced significantly higher levels of TNF-α, IL-10 and IL-15 production by cells challenged with the fungus. These results suggest a modulatory effect of IL-15 on pro and anti-inflammatory cytokine production, oxidative metabolism and fungicidal activity of monocytes during Pb18 infection.
Departamento de Microbiologia e Imunologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brasil. cfbannwart@ibb.unesp.br
Camila Ferreira
CF
Bannwart
Rosana A Rodrigues
RA
Martins
Erika
E
Nakaira-Takahashi
Luciane A
LA
Dias-Melício
Angela M V Campos
AM
Soares
Maria Terezinha S
MT
Peraçoli
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D019409:Interleukin-15 / Q000494:pharmacology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010228:Paracoccidioides / Q000254:growth & development / Q000276:immunology*; D013481:Superoxides / Q000097:blood*; D055815:Young Adult
D016207:Cytokines; D019409:Interleukin-15; D013481:Superoxides; D006861:Hydrogen Peroxide