deconvolution of the response to bacillus calmette–guérin reveals nf-κb-induced cytokines as autocrine mediators of innate immunity

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ID: 133711
2017
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Abstract
Bacillus Calmette–Guérin (BCG) is used as a vaccine and diagnostic test for tuberculosis, as well as immunotherapy in the treatment of bladder cancer. While clinically useful, the response to mycobacterial stimulation is complex and the induced protein signature remains poorly defined. We characterized the cell types directly engaged by BCG, as well as the induced cytokine loops that transmit signal(s) to bystander cells. Standardized whole-blood stimulations and mechanistic studies on single and purified cell populations identified distinct patterns of activation in monocytes as compared to neutrophils and invariant lymphocyte populations. Deconvoluting the role of Toll-like receptor 2/4 and Dectin-1/2 in the inflammatory response to BCG, we revealed Dectin-1/2 as dominant in neutrophils as compared to monocytes, which equally engaged both pathways. Furthermore, we quantified the role of NF-κB and NADPH/reactive oxygen species (ROS)-dependent cytokines, which triggered a JAK1/2-dependent amplification loop and accounted for 40–50% of the induced response to BCG. In sum, this study provides new insight into the molecular and cellular pathways involved in the response to BCG, establishing the basis for a new generation of immunodiagnostic tools.
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bisiaux2017frontiersdeconvolution Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Aurélie Bisiaux;Aurélie Bisiaux;Jeremy Boussier;Jeremy Boussier;Jeremy Boussier;Darragh Duffy;Darragh Duffy;Lluis Quintana-Murci;Lluis Quintana-Murci;Magnus Fontes;Matthew L. Albert;Matthew L. Albert;Matthew L. Albert;The Milieu Intérieur Consortium
Journal sudebno-meditsinskaia ekspertiza
Year 2017
DOI
10.3389/fimmu.2017.00796
URL
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00796/full
Keywords
immune monitoring toll-like receptors mycobacteria allergy

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