TY  - JOUR
N1  - Copyright of this article belongs to Oxford University Press.
ID  - open1696
UR  - http://jid.oxfordjournals.org/content/209/9/1436.long
IS  - 9
A1  - Siddiqui, Kaneez F
A1  - Amir, Mohammed
A1  - Gurram, Rama Krishna
A1  - Khan, Nargis
A1  - Arora, Ashish
A1  - Rajagopal, Kammara
A1  - Agrewala, J N
Y1  - 2014/05/01/
N2  - 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-?B 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.
PB  - Oxford University Press
JF  - The Journal of infectious diseases
VL  - 209
KW  - Mycobacterium tuberculosis; Acr1: alpha crystallin antigen; dendritic cells; immunosuppression 
SN  - 1537-6613
TI  - Latency-associated protein Acr1 impairs dendritic cell maturation and functionality: a possible mechanism of immune evasion by Mycobacterium tuberculosis.
SP  - 1436
EP  - 45
ER  -