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NLRP3 inflammasome activation by mycobacterial ESAT-6 and dsRNA in intraocular tuberculosis

Basu, S; Fowler, B; Kerur, N; Arnvig, KB; Rao, NA; (2018) NLRP3 inflammasome activation by mycobacterial ESAT-6 and dsRNA in intraocular tuberculosis. Microbial Pathogenesis , 114 pp. 219-224. 10.1016/j.micpath.2017.11.044. Green open access

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Abstract

The molecular basis of intraocular tuberculosis (TB) is not well understood. In this study, we investigated the role of two constituents of viable Mycobacterium tuberculosis - Early Secreted Antigenic Target-6 (ESAT-6), and mycobacterial RNA- in inflammasome activation in the retinal pigment epithelium (RPE) - a key site of inflammation in intraocular TB. We found that ESAT-6 induced caspase-1 activation and inflammasome priming in mouse RPE cells, significantly more in wild-type than in Tlr2/3/4/7/9-/-, Myd88-/- and Nlrp3-/- RPE cells. Sub-retinal ESAT-6 injection resulted in greater RPE degeneration in wild-type than Nlrp3-/- mice. In human ocular TB tissue sections, NLRP3 staining was noted in retina as well as RPE. Mycobacterial RNA, specifically its double stranded component, also induced caspase-1 activation, and the double stranded RNA was immunolocalized to human ocular TB sections. Our observations suggest that inflammasome activation in RPE by viable M. tuberculosis could potentially contribute to human intraocular TB.

Type: Article
Title: NLRP3 inflammasome activation by mycobacterial ESAT-6 and dsRNA in intraocular tuberculosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.micpath.2017.11.044
Publisher version: http://dx.doi.org/10.1016/j.micpath.2017.11.044
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ESAT-6, Inflammasome, Intraocular tuberculosis, NLRP3, RNA
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10039977
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