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Published on: March 16, 2018
Interleukin-15 increases Paracoccidioides brasiliensis killing by human neutrophils
Elisandra Garcia Tavian1, Luciane Alarcão Dias-Melicio, Michele Janegitz Acorci
1Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, CEP 18618-000, S.P., Brazil.
Abstract:
Interleukin-15 is a cytokine produced by a wide range of different cell types, including macrophages, in response to lipopolysaccharide or microbial infection. This cytokine may play a crucial role in the activation of phagocytic cells against pathogens, especially during innate immune response. The effects of IL-15 on human polymorphonuclear leukocyte fungicidal activity against a highly virulent Paracoccidioides brasiliensis strain were investigated. Pretreatment of human neutrophils from healthy individuals with IL-15 for 18 hours increased cell fungicidal activity in a dose-dependent manner. In addition, the exposure to IL-15 induced an increase in neutrophil oxidative burst as evaluated by superoxide anion and H(2)O(2) release. Catalase inhibited fungicidal activity supporting a role for H(2)O(2) in fungus killing. In contrast, IL-8 and TNF-alpha levels were not affected by IL-15 suggesting that its effects were not mediated by these cytokines. Together, these results show that IL-15 is a potent stimulant of antifungal activities in human neutrophils, at least in part by a mechanism dependent on oxidative metabolism.
Insights
Interleukin-15 (IL-15) enhances human neutrophil antifungal activity against Paracoccidioides brasiliensis. This cytokine boosts neutrophil oxidative burst, crucial for pathogen killing, without affecting IL-8 or TNF-alpha levels.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Interleukin-15 (IL-15) is a cytokine produced by various cells, including macrophages.
- IL-15 plays a role in innate immune responses and phagocytic cell activation against pathogens.
- The specific impact of IL-15 on human neutrophil fungicidal activity was not fully elucidated.
Purpose of the Study:
- To investigate the effects of IL-15 on human polymorphonuclear leukocyte (neutrophil) fungicidal activity.
- To determine if IL-15 influences the oxidative burst of neutrophils.
- To explore the mechanism underlying IL-15's effect on neutrophil antifungal capacity.
Main Methods:
- Human neutrophils from healthy donors were pretreated with varying doses of IL-15.
- Fungicidal activity against a virulent strain of Paracoccidioides brasiliensis was assessed.
- Neutrophil oxidative burst was measured via superoxide anion and hydrogen peroxide (H2O2) release.
- The role of H2O2 was examined using catalase inhibition.
- Levels of IL-8 and TNF-alpha were monitored.
Main Results:
- Pretreatment with IL-15 significantly increased neutrophil fungicidal activity in a dose-dependent manner.
- IL-15 exposure led to enhanced neutrophil oxidative burst, evidenced by increased superoxide anion and H2O2 release.
- Catalase treatment inhibited the fungicidal activity, confirming the role of H2O2 in killing Paracoccidioides brasiliensis.
- IL-15 did not affect the levels of IL-8 and TNF-alpha.
Conclusions:
- Interleukin-15 is a potent stimulant of antifungal activity in human neutrophils.
- The mechanism involves, at least partly, an enhancement of the oxidative metabolism and H2O2 production.
- IL-15's effects are not mediated through increased IL-8 or TNF-alpha.
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