Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.

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 i...

Full description

Saved in:
Bibliographic Details
Main Authors: Shibali Das, Sayantan Banerjee, Saikat Majumder, Bidisha Paul Chowdhury, Avranil Goswami, Kuntal Halder, Urmita Chakraborty, Nishith K Pal, Subrata Majumdar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092477&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850191367703101440
author Shibali Das
Sayantan Banerjee
Saikat Majumder
Bidisha Paul Chowdhury
Avranil Goswami
Kuntal Halder
Urmita Chakraborty
Nishith K Pal
Subrata Majumdar
author_facet Shibali Das
Sayantan Banerjee
Saikat Majumder
Bidisha Paul Chowdhury
Avranil Goswami
Kuntal Halder
Urmita Chakraborty
Nishith K Pal
Subrata Majumdar
author_sort Shibali Das
collection DOAJ
description 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.
format Article
id doaj-art-9bafd0bd140644afb5437c52f473faab
institution OA Journals
issn 1932-6203
language English
publishDate 2014-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-9bafd0bd140644afb5437c52f473faab2025-08-20T02:14:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9247710.1371/journal.pone.0092477Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.Shibali DasSayantan BanerjeeSaikat MajumderBidisha Paul ChowdhuryAvranil GoswamiKuntal HalderUrmita ChakrabortyNishith K PalSubrata MajumdarTuberculosis 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092477&type=printable
spellingShingle Shibali Das
Sayantan Banerjee
Saikat Majumder
Bidisha Paul Chowdhury
Avranil Goswami
Kuntal Halder
Urmita Chakraborty
Nishith K Pal
Subrata Majumdar
Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
PLoS ONE
title Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
title_full Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
title_fullStr Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
title_full_unstemmed Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
title_short Immune subversion by Mycobacterium tuberculosis through CCR5 mediated signaling: involvement of IL-10.
title_sort immune subversion by mycobacterium tuberculosis through ccr5 mediated signaling involvement of il 10
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092477&type=printable
work_keys_str_mv AT shibalidas immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT sayantanbanerjee immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT saikatmajumder immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT bidishapaulchowdhury immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT avranilgoswami immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT kuntalhalder immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT urmitachakraborty immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT nishithkpal immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10
AT subratamajumdar immunesubversionbymycobacteriumtuberculosisthroughccr5mediatedsignalinginvolvementofil10