Siddiqui, Kaneez F and Amir, Mohammed and Gurram, Rama Krishna and Khan, Nargis and Arora, Ashish and Rajagopal, Kammara and Agrewala, J N (2014) Latency-associated protein Acr1 impairs dendritic cell maturation and functionality: a possible mechanism of immune evasion by Mycobacterium tuberculosis. The Journal of infectious diseases, 209 (9). pp. 1436-45. ISSN 1537-6613
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Mycobacterium tuberculosis (M. tuberculosis) in latently infected individuals survives and thwarts the attempts of eradication by the immune system. During latency, Acr1 is predominantly expressed by the bacterium. However, whether M. tuberculosis exploits its Acr1 in impairing the host immunity remains widely unexplored. Hence, currently we have investigated the role of Acr1 in influencing the differentiation and function of dendritic cells (DCs), which play a cardinal role in innate and adaptive immunity. Therefore, for the first time, we have revealed a novel mechanism of mycobacterial Acr1 in inhibiting the maturation and differentiation of DCs by inducing tolerogenic phenotype by modulating the expression of PD-L1; Tim-3; indoleamine 2, 3-dioxygenase (IDO); and interleukin 10. Furthermore, Acr1 interferes in the differentiation of DCs by targeting STAT-6 and STAT-3 pathways. Continuous activation of STAT-3 inhibited the translocation of NF-κB in Acr1-treated DCs. Furthermore, Acr1 also augmented the induction of regulatory T cells. These DCs displayed decline in their antigen uptake capacity and reduced ability to help T cells. Interestingly, M. tuberculosis exhibited better survival in Acr1-treated DCs. Thus, this study provides a crucial insight into a strategy adopted by M. tuberculosis to survive in the host by impairing the function of DCs.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Oxford University Press. |
| Uncontrolled Keywords: | Mycobacterium tuberculosis; Acr1: alpha crystallin antigen; dendritic cells; immunosuppression |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 20 Jul 2015 04:24 |
| Last Modified: | 22 Jul 2015 04:26 |
| URI: | http://crdd.osdd.net/open/id/eprint/1696 |
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