The MYD88-Independent Pathway Is Not Mobilized in Human Neutrophils Stimulated via TLR4

• DOI: 10.4049/jimmunol.178.11.7344
• Publication Date: 2014-04-18T23:24:11Z
• Authors: Nicola Tamassia; Vincent Le Moigne; Federica Calzetti; Marta Donini; Sara Gasperini; Thornin Ear; Alexandre Cloutier; Fernando O Martinez; Marco Fabbri; Massimo Locati; Alberto Mantovani; Patrick P McDonald; Marco A Cassatella
• Keywords: Lipopolysaccharides; 0301 basic medicine; Neutrophils; [SDV]Life Sciences [q-bio]; Inflammation ; LPS ; phagocyte ; signal transduction ; transcriptional profile; Cell Differentiation; HL-60 Cells; Interferon-beta; Monocytes; Neutrophil Activation; Cell Line; 3. Good health; neutrophils; lipopolysaccharide (LPS); inflammation; TLR4; [SDV] Life Sciences [q-bio]; Chemokine CXCL10; Toll-Like Receptor 4; 03 medical and health sciences; Gene Expression Regulation; Myeloid Differentiation Factor 88; Humans; Chemokines, CXC; Cells, Cultured; Signal Transduction

Abstract LPS activates both MyD88-dependent and -independent signaling via TLR4, but the extent to which each cascade is operative in different cell types remains unclear. This prompted us revisit intriguing issue of CXCL10 production, we previously showed be inducible neutrophils stimulated with IFN-γ not either stimulus alone, contrary other myeloid cells. We now report that MyD88-independent pathway activated by LPS. Indeed, microarray real-time PCR experiments neither IFNβ nor IFNβ-dependent genes (including CXCL10) are LPS-treated neutrophils, contrast monocytes. Further investigation into inability promote expression revealed transcription factors regulating enhanceosome, such as IFN-regulatory factor-3 AP-1, lack dimerization, nuclear translocation, confocal microscopy, binding DNA. Moreover, show upstream TANK-binding kinase-1 neutrophils. A IFNβ/CXCL10 mRNA factor 3 activation was also observed leukemia HL60 cells differentiated granulocytes then LPS, indicating activate represents a feature their terminal maturation. These results identify disconnected two pathways downstream TLR4 key cellular components inflammatory immune responses help better understand primordial role host defense against nonviral infections.