Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity.
Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens.
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Nargis
N
Khan
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Mohammad
M
Aqdas
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Aurobind
A
Vidyarthi
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Shikha
S
Negi
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Susanta
S
Pahari
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Tapan
T
Agnihotri
CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA.
Javed N
JN
Agrewala
D056704:Adaptive Immunity; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D051379:Mice; D009161:Mycobacterium / Q000254:growth & development; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
D016898:Interferon-alpha; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D050791:STAT Transcription Factors; D016899:Interferon-beta