Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells.
Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range of different cell types including fibroblasts, keratinocytes, endothelial cells, and macrophages in response to lipopolysaccharide or microbial infection. This suggests that IL-15 may play a crucial role in the activation of phagocytic cells against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL-15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8 production, following stimulation with the cytokine. The PMN response to IL-15 depends on binding to the IL-15 receptor. Our experiments show that binding of a biotinylated human IL-15-immunoglobulin G2b IgG2b fusion protein was competed by the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting that IL-15 binding to PMN might involve the IL-2Rbeta and IL-2Rgamma chains, which have been shown to be constitutively expressed by PMN. In addition, we show by reverse transcription-PCR and by flow cytometry with a specific anti-IL-15Ralpha chain monoclonal antibody that PMN express the IL-15Ralpha chain at the mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the chemotactic factor IL-8, and the amount secreted was increased by costimulation with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not sufficient to trigger the respiratory burst or to increase the production of superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN to phagocytose heat-killed C. albicans organisms in a dose-dependent manner, without opsonization by antibodies or complement-derived products. In the same concentration range, IL-15 was as effective as gamma interferon (IFN-gamma) and IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken together, these results suggest that IL-15 is a potent stimulant of both proinflammatory and antifungal activities of PMN, activating several antimicrobial functions of PMN involved in the cellular response against C. albicans.
Musso
T
T
Department of Public Health and Microbiology, University of Turin, Turin, Italy.
Calosso
L
L
Zucca
M
M
Millesimo
M
M
Puliti
M
M
Bulfone-Paus
S
S
Merlino
C
C
Savoia
D
D
Cavallo
R
R
Ponzi
A N
AN
Badolato
R
R
D002176:Candida albicans / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding; D013481:Superoxides / Q000378:metabolism
D019409:Interleukin-15; D016209:Interleukin-8; D013481:Superoxides