Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.

<h4>Background</h4>Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective respon...

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Autores principales:	Nasir Salam, Shashank Gupta, Sachin Sharma, Shweta Pahujani, Aprajita Sinha, Rajiv K Saxena, Krishnamurthy Natarajan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bcbcc6eae46e4882bb65b8d61deb26f8
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spelling	oai:doaj.org-article:bcbcc6eae46e4882bb65b8d61deb26f82021-11-25T06:11:21ZProtective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.1932-620310.1371/journal.pone.0002869https://doaj.org/article/bcbcc6eae46e4882bb65b8d61deb26f82008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18682728/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs).<h4>Methods and findings</h4>Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment.<h4>Conclusions</h4>These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection.Nasir SalamShashank GuptaSachin SharmaShweta PahujaniAprajita SinhaRajiv K SaxenaKrishnamurthy NatarajanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2869 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nasir Salam Shashank Gupta Sachin Sharma Shweta Pahujani Aprajita Sinha Rajiv K Saxena Krishnamurthy Natarajan Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
description	<h4>Background</h4>Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs).<h4>Methods and findings</h4>Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment.<h4>Conclusions</h4>These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection.
format	article
author	Nasir Salam Shashank Gupta Sachin Sharma Shweta Pahujani Aprajita Sinha Rajiv K Saxena Krishnamurthy Natarajan
author_facet	Nasir Salam Shashank Gupta Sachin Sharma Shweta Pahujani Aprajita Sinha Rajiv K Saxena Krishnamurthy Natarajan
author_sort	Nasir Salam
title	Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
title_short	Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
title_full	Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
title_fullStr	Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
title_full_unstemmed	Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.
title_sort	protective immunity to mycobacterium tuberculosis infection by chemokine and cytokine conditioned cfp-10 differentiated dendritic cells.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/bcbcc6eae46e4882bb65b8d61deb26f8
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Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.

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