Y the mycobacterial surface lipid PGL enables bacterial escape by inducing the recruitment of mycobacteriumpermissive monocytes via the CCL2CCR2 chemokine axis. Their findings reveal a relocation tactic that allows mycobacterial dissemination, and argue for the potential of interventions focusing on PGL in the prevention of tuberculosis.HighlightsdMicrobicidal tissue-resident macrophages are 1st responders to mycobacteria Mycobacterial phenolic glycolipid induces macrophage CCL2 by STING activation CCL2 recruits mycobacterium-permissive monocytes to your tissue-resident macrophage Mycobacteria transfer from tissue macrophage to monocyte by a cell fusion eventdddCambier et al., 2017, Immunity 47, 55265 September 19, 2017 2017 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.immuni.2017.08.ImmunityArticlePhenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident MacrophagesC.J. Cambier,1,2,three Seonadh M. O’Leary,four Mary P. O’Sullivan,four Joseph Keane,4,* and Lalita Ramakrishnan1,2,five,6,seven,*of Immunology, University of Washington, Seattle, WA 98195, USA Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, Uk 3Department of Chemistry, Stanford University, Stanford, CT 94305, USA 4Department of Clinical Medication, Trinity Translational Medication Institute, Trinity University Dublin, Dublin 8, Ireland 5Department of Microbiology, University of Washington, Seattle, WA 98195, USA 6Department of Medication, University of Washington, Seattle, WA 98195, USA 7Lead Get in touch with *Correspondence: [email protected] (J.K.), [email protected] kingdom (L.R.) http://dx.doi.org/10.1016/j.immuni.2017.08.2Molecular 1DepartmentSUMMARYMycobacterium tuberculosis (Mtb) enters the host in aerosol droplets deposited in lung alveoli, exactly where the bacteria initial encounter lung-resident alveolar macrophages. We studied the earliest mycobacteriummacrophage interactions while in the optically transparent zebrafish.Mangiferin medchemexpress First-responding resident macrophages phagocytosed and eradicated infecting mycobacteria, suggesting that to create an effective infection, mycobacteria ought to escape from the at first infected resident macrophage into growth-permissive monocytes. We defined a crucial part for mycobacterial membrane phenolic glycolipid (PGL) in engineering this transition. PGL activated the STING cytosolic sensing pathway in resident macrophages, inducing the production in the chemokine CCL2, which in flip recruited circulating CCR2+ monocytes towards infection.Anrukinzumab Description Transient fusion of contaminated macrophages with CCR2+ monocytes enabled bacterial transfer and subsequent dissemination, and interrupting this transfer so as to prolong mycobacterial sojourn in resident macrophages promoted clearing of infection.PMID:22943596 Human alveolar macrophages made CCL2 within a PGL-dependent vogue following infection, arguing for your possible of PGL-blocking interventions or PGL-targeting vaccine tactics within the prevention of tuberculosis.INTRODUCTION When M. tuberculosis (Mtb) is aerosolized into the decrease lung, it first encounters lung-resident alveolar macrophages that patrol the air-lung epithelium interface (Srivastava et al., 2014). While in the 1st few days post-infection, Mtb is identified exclusively within alveolar macrophages (Srivastava et al., 2014; Urdahl, 2014; Wolfet al., 2007). Thereafter, it traverses the lung epithelium to reside inside other myeloid cells that have aggregated into granulomas (Cambier et al., 2014a;.