Interleukin 1 alpha (IL-1 alpha) restricts Brucella abortus 544 survival through promoting lysosomal-mediated killing and NO production in macrophages

Abstract

The interleukin-1 (IL-1) family of cytokines, particularly IL-1 alpha and IL-1 beta, are potent regulators of innate immunity that play key roles in host defense against infection, hence we evaluated the role of these cytokines in the control of brucellosis within RAW 264.7 cells. Marked expression and secretion of IL-1 alpha and IL-1 beta were observed during Brucella infection in macrophages. Blocking of IL-1 alpha and IL-1 beta reduced induction of IL-10, IL-1 beta and TNF, and IL-6 and TNF, respectively. However, interference of IL-1 alpha and not IL-1 beta signaling notably augmented susceptibility of macrophages to Brucella infection which indicates that IL-1 alpha is required for a downstream signaling cascade of innate immunity for efficient clearance of Brucella. This protection requires binding to interleukin-1 receptor (IL-1R) mediated by myeloid differentiation factor 88 (MyD88) signaling and associated with increased lysosomal-mediated killing and nitric oxide (NO) production. Expression of pro-inflammatory cytokines was observed to be mediated via NF-kappa B-p50, HIF-1 alpha and CEBPA, but negatively controlled by CEBPB while transcription of some important phagolysosomal genes was regulated via CEBPA and c-Jun which indicates the important role of these transcription factors in the control of Brucella infection in macrophages via IL-1 alpha signaling pathway.