ISG15 induces IL-10 production in human monocytes and is a biomarker of disease severity during active tuberculosis

• DOI: 10.17863/cam.38046
• Publication Date: 2017-07-21
• Authors: Paula Fernandes d...; Johan Van Weyenbergh; Murilo Delgobo; Daniel de Oliveir...; Brian J. Ferguson; Rodrigo Guabiraba; Tim Dierckx; Soraya Maria Menezes; André Báfica; Daniel Santos Mansur
• Keywords: ISG15; Ex vivo; Monocyte

Interferon stimulated gene 15 (ISG15) deficiency in humans leads to severe interferonopathies and mycobacterial disease, the latter being previously associated its extracellular cytokine-like activity. Here, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique human primary monocytes. Employing ex vivo systems analysis of transcriptome datasets, observed significant correlation ISG15-induced monocyte lymphocyte IFNγ balanced expression. This effect was with p38 MAPK PI3K signalling healthy volunteers. The specificity MAPK/PI3K-dependence production confirmed vitro using CRISPR/Cas9 knockout pharmacological inhibitors. Moreover, this ISG15/IL10 axis amplified leprosy but disrupted active tuberculosis (TB) patients. Importantly, strongly correlated inflammation disease severity during TB. In conclusion, study identifies anti-inflammatory ISG15/IL-10 myeloid that is TB, revealing potential biomarker major disease.