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Mycobacterium bovis Bacille Calmette-Guerin infection modulates GRK2/3 dependent cytokine secretion


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.


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.


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.


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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Correspondence to Manisha Yadav.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( 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).

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