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2013-06-29Zeitschriftenartikel DOI: 10.1016/j.cyto.2013.06.310
Dormancy Associated Translation Inhibitor (DATIN/Rv0079) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression
dc.contributor.authorKumar, Ashutosh
dc.contributor.authorLewin, Astrid
dc.contributor.authorRani, Pittu Sandhya
dc.contributor.authorQureshi, Insaf A.
dc.contributor.authorDevi, Savita
dc.contributor.authorMajid, Mohammad
dc.contributor.authorKamal, Elisabeth
dc.contributor.authorMarek, Stefanie
dc.contributor.authorHasnain, Seyed E.
dc.contributor.authorAhmed, Niyaz
dc.date.accessioned2018-05-07T17:51:38Z
dc.date.available2018-05-07T17:51:38Z
dc.date.created2014-08-19
dc.date.issued2013-06-29none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/regXRkq7QzyDY/PDF/2218UTsdMqEE.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1938
dc.description.abstractMycobacterium tuberculosis, the cause of tuberculosis in humans, is present approximately in one third of the world’s population, mostly in a dormant state. The proteins encoded by the dormancy survival regulon (DosR regulon) are mainly responsible for survival of the bacilli in a latent form. To maintain latency, mycobacteria orchestrate a balanced interplay of different cytokines secreted by immune cells during the granulomatous stage. The function of most of the DosR regulon proteins of M. tuberculosis is unknown. In this study, we have shown that one of the DosR regulon proteins, DATIN, encoded by the gene Rv0079, can stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. The expression level of DATIN in Mycobacterium bovis BCG was found to be upregulated in pH stress and microaerobic conditions. Computational modeling, docking and simulation study suggested that DATIN might interact with TLR2. This was further confirmed through the interaction of recombinant DATIN with TLR2 expressed by HEK293 cells. When in vitro differentiated THP-1 cells were treated with recombinant DATIN, increased secretion of TNF-α, IL-1β and IL-8 was observed in a dose dependent manner. When differentiated THP-1 cells were infected with a modified BCG strain that overexpressed DATIN, augmented secretions of TNF-α, IL-1β and IL-8 were observed as compared to a reference BCG strain containing empty vector. Similarly, human PBMCs when infected with M. bovis BCG that overexpressed DATIN, upregulated secretion of proinflammatory cytokines IFN-γ, TNF-α, IL-1β and IL-8. The cytokine profiles dissected herein point to a possible role of DATIN in maintenance of latency with the help of the proinflammatory responses.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectMycobacterium tuberculosiseng
dc.subjectDormancy antigenseng
dc.subjectDosR regulon proteinseng
dc.subjectProinflammatory cytokineseng
dc.subjectTLR2eng
dc.subject.ddc610 Medizin
dc.titleDormancy Associated Translation Inhibitor (DATIN/Rv0079) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10037269
dc.identifier.doi10.1016/j.cyto.2013.06.310
dc.identifier.doihttp://dx.doi.org/10.25646/1863
local.edoc.container-titleCytokine
local.edoc.container-textKumar, A., Lewin, A., Rani, P.S., Qureshi, I.A., Devi, S., Majid, M., Kamal, E., Marek, S., Hasnain, S.E., Ahmed, N. Dormancy Associated Translation Inhibitor (DATIN/Rv0079) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression (2013) Cytokine, 64 (1), pp. 258-264.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.sciencedirect.com/science/article/pii/S104346661300584X
local.edoc.container-publisher-nameElsevier
local.edoc.container-volume64
local.edoc.container-issue1
local.edoc.container-year2013

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