Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence.
Monocyte dysfunction by filarial antigens has been a major mechanism underlying immune evasion following hyporesponsiveness during patent lymphatic filariasis. Recent studies have initiated a paradigm shift to comprehend the immunological interactions of Wolbachia and its antigens in inflammation, a...
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ftdoajarticles:oai:doaj.org/article:7d455deb4d494fe1a629d37684a72bd7 2023-05-15T15:09:20+02:00 Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. Vijayan Kamalakannan Abijit Shiny Subash Babu Rangarajan Badri Narayanan 2015-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003675 https://doaj.org/article/7d455deb4d494fe1a629d37684a72bd7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4388636?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003675 https://doaj.org/article/7d455deb4d494fe1a629d37684a72bd7 PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003675 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003675 2022-12-31T12:03:17Z Monocyte dysfunction by filarial antigens has been a major mechanism underlying immune evasion following hyporesponsiveness during patent lymphatic filariasis. Recent studies have initiated a paradigm shift to comprehend the immunological interactions of Wolbachia and its antigens in inflammation, apoptosis, lymphocyte anergy, etc. Here we showed that recombinant Wolbachia heat shock protein 60 (rWmhsp60) interacts with TLR-4 and induces apoptosis in monocytes of endemic normal but not in chronic patients. Higher levels of reactive oxygen species (ROS) induced after TLR-4 stimulation resulted in loss of mitochondrial membrane potential and caspase cascade activation, which are the plausible reason for apoptosis. Furthermore, release in ROS owing to TLR-4 signaling resulted in the activation of NF-κB p65 nuclear translocation which leads to inflammation and apoptosis via TNF receptor pathway following the increase in IL-6 and TNF-α level. Here for the first time, we report that in addition to apoptosis, rWmhsp60 antigen in filarial pathogenesis also induces molecular senescence in monocytes. Targeting TLR-4, therefore, presents a promising candidate for treating rWmhsp60-induced apoptosis and senescence. Strikingly, induction of autophagy by rapamycin detains TLR-4 in late endosomes and subverts TLR-4-rWmhsp60 interaction, thus protecting TLR-4-mediated apoptosis and senescence. Furthermore, rapamycin-induced monocytes were unresponsive to rWmhsp60, and activated lymphocytes following PHA stimulation. This study demonstrates that autophagy mediates the degradation of TLR-4 signaling and protects monocytes from rWmhsp60 induced apoptosis and senescence. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 4 e0003675 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Vijayan Kamalakannan Abijit Shiny Subash Babu Rangarajan Badri Narayanan Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Monocyte dysfunction by filarial antigens has been a major mechanism underlying immune evasion following hyporesponsiveness during patent lymphatic filariasis. Recent studies have initiated a paradigm shift to comprehend the immunological interactions of Wolbachia and its antigens in inflammation, apoptosis, lymphocyte anergy, etc. Here we showed that recombinant Wolbachia heat shock protein 60 (rWmhsp60) interacts with TLR-4 and induces apoptosis in monocytes of endemic normal but not in chronic patients. Higher levels of reactive oxygen species (ROS) induced after TLR-4 stimulation resulted in loss of mitochondrial membrane potential and caspase cascade activation, which are the plausible reason for apoptosis. Furthermore, release in ROS owing to TLR-4 signaling resulted in the activation of NF-κB p65 nuclear translocation which leads to inflammation and apoptosis via TNF receptor pathway following the increase in IL-6 and TNF-α level. Here for the first time, we report that in addition to apoptosis, rWmhsp60 antigen in filarial pathogenesis also induces molecular senescence in monocytes. Targeting TLR-4, therefore, presents a promising candidate for treating rWmhsp60-induced apoptosis and senescence. Strikingly, induction of autophagy by rapamycin detains TLR-4 in late endosomes and subverts TLR-4-rWmhsp60 interaction, thus protecting TLR-4-mediated apoptosis and senescence. Furthermore, rapamycin-induced monocytes were unresponsive to rWmhsp60, and activated lymphocytes following PHA stimulation. This study demonstrates that autophagy mediates the degradation of TLR-4 signaling and protects monocytes from rWmhsp60 induced apoptosis and senescence. |
format |
Article in Journal/Newspaper |
author |
Vijayan Kamalakannan Abijit Shiny Subash Babu Rangarajan Badri Narayanan |
author_facet |
Vijayan Kamalakannan Abijit Shiny Subash Babu Rangarajan Badri Narayanan |
author_sort |
Vijayan Kamalakannan |
title |
Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
title_short |
Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
title_full |
Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
title_fullStr |
Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
title_full_unstemmed |
Autophagy protects monocytes from Wolbachia heat shock protein 60-induced apoptosis and senescence. |
title_sort |
autophagy protects monocytes from wolbachia heat shock protein 60-induced apoptosis and senescence. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003675 https://doaj.org/article/7d455deb4d494fe1a629d37684a72bd7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003675 (2015) |
op_relation |
http://europepmc.org/articles/PMC4388636?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003675 https://doaj.org/article/7d455deb4d494fe1a629d37684a72bd7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003675 |
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PLOS Neglected Tropical Diseases |
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9 |
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4 |
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e0003675 |
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