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Mycobacterium bovis Bacille Calmette-Guerin infection modulates GRK2/3 dependent cytokine secretion
BMC Infectious Diseases volume 14, Article number: E20 (2014)
Background
Mycobacterium tuberculosis has evolved highly specialized mechanisms to proliferate in the host during infection. In this process, the infection of alveolar epithelial cells is a necessary step for mycobacteria dissemination; however the mechanisms of mycobacterial epithelial interactions are incompletely understood. Previously, we characterized the role of epithelial G protein coupled receptors (GPCR) CXCR1 and CXCR2 during mycobacterial infection. However the role of GPCR kinases (GRK) 2/3 and GRK4-6 in response to mycobacterial infection has not been investigated.
Methods
The GPCR kinases expression (GRK2/3 and GRK4-6) after Mycobacterium infection was quantified by RT-PCR and Western blot analysis. Further, the secretion of cytokines IL-8 and TNF-α was quantified in supernatants by ELISA.
Results
Mycobacterial infection in lung epithelial cells increased secretion of IL-8 and decreased TNF-α upto 72 hours. Further, the infection in the epithelial cells was modulated by a combined up regulation of GPCR kinases (GRK) 2/3 genes and suppression of the GRK 4-6 gene expression. These results were confirmed at protein levels. In addition, the blocking of chemokine receptors decreased the inhibition of GRK 2/3 expression suggesting that mycobacteria manipulate epithelial responses by desensitizing the receptors and the cytokine secretion.
Conclusions
In conclusion, we have identified a role for GRK 2/3 dependent cytokine secretion in the initial phase of mycobacterial infections in the lung epithelial cells.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Yadav, M., Nagarjuna, D. & Dhanda, R.S. Mycobacterium bovis Bacille Calmette-Guerin infection modulates GRK2/3 dependent cytokine secretion. BMC Infect Dis 14 (Suppl 3), E20 (2014). https://doi.org/10.1186/1471-2334-14-S3-E20
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DOI: https://doi.org/10.1186/1471-2334-14-S3-E20