IL-20 MODULATES INNATE IMMUNE RESPONSES OF HUMAN CELLS TO STAPHYLOCOCCUS AUREUS

As a leading cause of infection worldwide, Staphylococcus aureus is a versatile commensal microbe that can coexist with its host harmoniously and undetected, but is capable of causing invasive and life threatening infections. Due to its unusually extensive arsenal of factors that serve invasion of host tissues and evasion of the immune system, effective treatment and prevention measures for S. aureus have remained largely elusive for researchers. Efforts to understand the immune response to S. aureus have yielded an amalgam of findings, but a common thread throughout is the importance of neutrophils: both for their robust bactericidal functions and their ability to damage host tissue. ,Neutrophils possess multiple antimicrobial mechanisms that are critical for protection of the host against infection with S. aureus, as patients with defects in number or function of these cells are rendered vulnerable to staphylococcal infections. Recruitment and activation of neutrophils at sites of infection is driven by cytokine and chemokine signals that directly target neutrophils via specific cell surface receptors. The IL-20 subfamily of cytokines has been reported to act at epithelial sites and contribute to psoriasis, wound healing, and anti-inflammatory effects during cutaneous S. aureus infection. Adding to previous work that demonstrated the effects of IL-20 on human keratinocytes during infection with S. aureus, our results show that IL-20 is produced by human bronchial epithelial cells in response to S. aureus. Here, IL-20 modulated production of a key antimicrobial peptide and affected the pro-inflammatory signaling generated for recruitment of neutrophils. IL-20 and its related cytokines have been studied almost exclusively for their effects on epithelial cell function; however, the ability of these cytokines to directly affect neutrophil function remains incompletely understood. ,Here, we show that human neutrophils altered their expression of IL-20 receptor chains upon migration and activation in vivo and in vitro. Such activation of neutrophils under conditions mimicking infection with S. aureus conferred responsiveness to IL-20 that manifested as modification of actin polymerization and inhibition of a broad range of actin-dependent functions, including phagocytosis, granule exocytosis, and migration. Consistent with the previously described homeostatic and anti-inflammatory properties of IL-20 on epithelial cells, the current studies provide evidence that IL-20 directly targets and inhibits key inflammatory functions of neutrophils during infection with S. aureus.