Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating pro...

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Autores principales:	Shashank Gupta, Nasir Salam, Varsha Srivastava, Rupak Singla, Digamber Behera, Khalid U Khayyam, Reshma Korde, Pawan Malhotra, Rajiv Saxena, Krishnamurthy Natarajan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ff101c6cf15425e9fdbd7552a1bffc4
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spelling	oai:doaj.org-article:5ff101c6cf15425e9fdbd7552a1bffc42021-11-25T06:23:04ZVoltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.1932-620310.1371/journal.pone.0005305https://doaj.org/article/5ff101c6cf15425e9fdbd7552a1bffc42009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19390594/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.Shashank GuptaNasir SalamVarsha SrivastavaRupak SinglaDigamber BeheraKhalid U KhayyamReshma KordePawan MalhotraRajiv SaxenaKrishnamurthy NatarajanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5305 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shashank Gupta Nasir Salam Varsha Srivastava Rupak Singla Digamber Behera Khalid U Khayyam Reshma Korde Pawan Malhotra Rajiv Saxena Krishnamurthy Natarajan Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
description	Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.
format	article
author	Shashank Gupta Nasir Salam Varsha Srivastava Rupak Singla Digamber Behera Khalid U Khayyam Reshma Korde Pawan Malhotra Rajiv Saxena Krishnamurthy Natarajan
author_facet	Shashank Gupta Nasir Salam Varsha Srivastava Rupak Singla Digamber Behera Khalid U Khayyam Reshma Korde Pawan Malhotra Rajiv Saxena Krishnamurthy Natarajan
author_sort	Shashank Gupta
title	Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
title_short	Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
title_full	Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
title_fullStr	Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
title_full_unstemmed	Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.
title_sort	voltage gated calcium channels negatively regulate protective immunity to mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/5ff101c6cf15425e9fdbd7552a1bffc4
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Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.

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