PMID- 18682728
OWN - NLM
STAT- MEDLINE
DCOM- 20081218
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 8
DP  - 2008 Aug 6
TI  - Protective immunity to Mycobacterium tuberculosis infection by chemokine and 
      cytokine conditioned CFP-10 differentiated dendritic cells.
PG  - e2869
LID - 10.1371/journal.pone.0002869 [doi]
LID - e2869
AB  - BACKGROUND: 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). METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
FAU - Salam, Nasir
AU  - Salam N
AD  - Immunology Group, International Centre for Genetic Engineering and Biotechnology, 
      Aruna Asaf Ali Marg, New Delhi, India.
FAU - Gupta, Shashank
AU  - Gupta S
FAU - Sharma, Sachin
AU  - Sharma S
FAU - Pahujani, Shweta
AU  - Pahujani S
FAU - Sinha, Aprajita
AU  - Sinha A
FAU - Saxena, Rajiv K
AU  - Saxena RK
FAU - Natarajan, Krishnamurthy
AU  - Natarajan K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080806
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CFP-10 protein (71-85), Mycobacterium tuberculosis)
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - Chemokine CCL5/pharmacology
MH  - Chemokine CXCL10/immunology
MH  - Chemokines/*pharmacology
MH  - Cytokines/*pharmacology
MH  - Dendritic Cells/drug effects/*immunology
MH  - Humans
MH  - Inflammation/genetics/physiopathology
MH  - Mycobacterium bovis/immunology
MH  - Mycobacterium tuberculosis/*immunology
MH  - Peptide Fragments/immunology
MH  - Tuberculosis/*immunology
PMC - PMC2478708
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2008/08/07 09:00
MHDA- 2008/12/19 09:00
PMCR- 2008/08/06
CRDT- 2008/08/07 09:00
PHST- 2008/05/19 00:00 [received]
PHST- 2008/07/11 00:00 [accepted]
PHST- 2008/08/07 09:00 [pubmed]
PHST- 2008/12/19 09:00 [medline]
PHST- 2008/08/07 09:00 [entrez]
PHST- 2008/08/06 00:00 [pmc-release]
AID - 08-PONE-RA-04738R2 [pii]
AID - 10.1371/journal.pone.0002869 [doi]
PST - epublish
SO  - PLoS One. 2008 Aug 6;3(8):e2869. doi: 10.1371/journal.pone.0002869.