TY - JOUR
T1 - Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling
T2 - Involvement of IL-10
AU - Das, Shibali
AU - Banerjee, Sayantan
AU - Majumder, Saikat
AU - Paul Chowdhury, Bidisha
AU - Goswami, Avranil
AU - Halder, Kuntal
AU - Chakraborty, Urmita
AU - Pal, Nishith K.
AU - Majumdar, Subrata
N1 - Funding Information:
We acknowledge the Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi for providing fellowship to Shibali Das. We also acknowledge Mr. Prabal Gupta for technical assistance.
PY - 2014/4/2
Y1 - 2014/4/2
N2 - Tuberculosis is characterized by severe immunosuppression of the host macrophages, resulting in the loss of the host protective immune responses. During Mycobacterium tuberculosis infection, the pathogen modulates C-C Chemokine Receptor 5 (CCR5) to enhance IL-10 production, indicating the possible involvement of CCR5 in regulation of the host immune response. Here, we found that Mycobacterium infection significantly increased CCR5 expression in macrophages there by facilitating the activation of its downstream signaling. These events culminated in up-regulation of the immunosuppressive cytokine IL-10 production, which was further associated with the down-regulation of macrophage MHC-II expression along with the up-regulation of CCR5 expression via engagement of STAT-3 in a positive feedback loop. Treatment of macrophages with CCR5 specific siRNA abrogated the IL-10 production and restored MHCII expression. While, in vivo CCR5 silencing was also effective for the restoration of host immune responses against tuberculosis. This study demonstrated that CCR5 played a very critical role for the immune subversion mechanism employed by the pathogen.
AB - Tuberculosis is characterized by severe immunosuppression of the host macrophages, resulting in the loss of the host protective immune responses. During Mycobacterium tuberculosis infection, the pathogen modulates C-C Chemokine Receptor 5 (CCR5) to enhance IL-10 production, indicating the possible involvement of CCR5 in regulation of the host immune response. Here, we found that Mycobacterium infection significantly increased CCR5 expression in macrophages there by facilitating the activation of its downstream signaling. These events culminated in up-regulation of the immunosuppressive cytokine IL-10 production, which was further associated with the down-regulation of macrophage MHC-II expression along with the up-regulation of CCR5 expression via engagement of STAT-3 in a positive feedback loop. Treatment of macrophages with CCR5 specific siRNA abrogated the IL-10 production and restored MHCII expression. While, in vivo CCR5 silencing was also effective for the restoration of host immune responses against tuberculosis. This study demonstrated that CCR5 played a very critical role for the immune subversion mechanism employed by the pathogen.
UR - http://www.scopus.com/inward/record.url?scp=84898796213&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0092477
DO - 10.1371/journal.pone.0092477
M3 - Article
C2 - 24695099
AN - SCOPUS:84898796213
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 4
M1 - e92477
ER -