creators_name: Siddiqui, Kaneez F
creators_name: Amir, Mohammed
creators_name: Gurram, Rama Krishna
creators_name: Khan, Nargis
creators_name: Arora, Ashish
creators_name: Rajagopal, Kammara
creators_name: Agrewala, J N
type: article
datestamp: 2015-07-20 04:24:43
lastmod: 2015-07-22 04:26:26
metadata_visibility: show
title: Latency-associated protein Acr1 impairs dendritic cell maturation and functionality: a possible mechanism of immune evasion by Mycobacterium tuberculosis.
ispublished: pub
subjects: QR
keywords: Mycobacterium tuberculosis; Acr1: alpha crystallin antigen; dendritic cells; immunosuppression 
note: Copyright of this article belongs to Oxford University Press.
abstract: 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.
date: 2014-05-01
date_type: published
publication: The Journal of infectious diseases
volume: 209
number: 9
publisher: Oxford University Press
pagerange: 1436-45
refereed: TRUE
issn: 1537-6613
official_url: http://jid.oxfordjournals.org/content/209/9/1436.long
citation:   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