Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Interleukin-15 (IL-15) is a cytokine produced by various cells in response to infection.
• IL-15 is implicated in the activation of phagocytic cells against pathogens.
• Polymorphonuclear leukocytes (PMNs) are key immune cells involved in pathogen defense.

Purpose of the Study:

• To investigate the activation of PMNs by IL-15.
• To evaluate the effect of IL-15 on PMN anti-Candida activity and IL-8 production.
• To elucidate the mechanism of IL-15 binding to PMNs.

Main Methods:

• Studied PMN activation by IL-15, assessing anti-Candida activity and IL-8 production.
• Investigated IL-15 receptor binding on PMNs using biotinylated IL-15-IgG2b fusion protein.
• Analyzed IL-15Ralpha chain expression on PMNs via RT-PCR and flow cytometry.
• Assessed PMN metabolic burst, respiratory burst, and phagocytosis of Candida albicans.

Main Results:

• IL-15 binding to PMNs involves IL-2Rbeta and IL-2Rgamma chains and the IL-15Ralpha chain.
• IL-15 stimulated PMNs to secrete IL-8, with enhanced secretion upon co-stimulation with Candida albicans.
• IL-15 primed PMN metabolic burst and increased phagocytosis of Candida albicans.
• IL-15 enhanced PMN's ability to inhibit Candida albicans growth, comparable to IFN-gamma and IL-2.

Conclusions:

• IL-15 is a potent stimulant of PMN proinflammatory and antifungal activities.
• IL-15 activates multiple PMN antimicrobial functions against Candida albicans.
• IL-15 plays a significant role in the cellular immune response against C. albicans.