Logo of Robert Koch InstituteLogo of Robert Koch Institute
Publication Server of Robert Koch Instituteedoc
de|en
View Item 
  • edoc-Server Home
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • View Item
  • edoc-Server Home
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.
All of edoc-ServerCommunity & CollectionTitleAuthorSubjectThis CollectionTitleAuthorSubject
PublishLoginRegisterHelp
StatisticsView Usage Statistics
All of edoc-ServerCommunity & CollectionTitleAuthorSubjectThis CollectionTitleAuthorSubject
PublishLoginRegisterHelp
StatisticsView Usage Statistics
View Item 
  • edoc-Server Home
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • View Item
  • edoc-Server Home
  • Artikel in Fachzeitschriften
  • Artikel in Fachzeitschriften
  • View Item
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
Kumar, Ashutosh
Lewin, Astrid
Rani, Pittu Sandhya
Qureshi, Insaf A.
Devi, Savita
Majid, Mohammad
Kamal, Elisabeth
Marek, Stefanie
Hasnain, Seyed E.
Ahmed, Niyaz
Mycobacterium 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.
Files in this item
Thumbnail
2218UTsdMqEE.pdf — Adobe PDF — 851.0 Kb
MD5: 63131bdd6bd8938d66c9557cd2d30ffa
Cite
BibTeX
EndNote
RIS
No license information
Details
Terms of Use Imprint Policy Data Privacy Statement Contact

The Robert Koch Institute is a Federal Institute

within the portfolio of the Federal Ministry of Health

© Robert Koch Institute

All rights reserved unless explicitly granted.

 
DOI
10.1016/j.cyto.2013.06.310
Permanent URL
https://doi.org/10.1016/j.cyto.2013.06.310
HTML
<a href="https://doi.org/10.1016/j.cyto.2013.06.310">https://doi.org/10.1016/j.cyto.2013.06.310</a>