PMID- 27265209 OWN - NLM STAT- MEDLINE DCOM- 20180424 LR - 20191210 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Jun 6 TI - Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity. PG - 27263 LID - 10.1038/srep27263 [doi] LID - 27263 AB - Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naive 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-alphabeta 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. FAU - Khan, Nargis AU - Khan N AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Aqdas, Mohammad AU - Aqdas M AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Vidyarthi, Aurobind AU - Vidyarthi A AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Negi, Shikha AU - Negi S AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Pahari, Susanta AU - Pahari S AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Agnihotri, Tapan AU - Agnihotri T AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. FAU - Agrewala, Javed N AU - Agrewala JN AD - CSIR-Institute of Microbial Technology, Chandigarh, 160036, INDIA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160606 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Interferon-alpha) RN - 0 (Nod2 Signaling Adaptor Protein) RN - 0 (Nod2 protein, mouse) RN - 0 (STAT Transcription Factors) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Adaptive Immunity MH - Animals MH - Bone Marrow Cells/*cytology/*immunology/metabolism/microbiology MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*cytology/*immunology/metabolism/microbiology MH - Immunity, Innate MH - Interferon-alpha/metabolism MH - Interferon-beta/metabolism MH - Mice MH - Mycobacterium/growth & development MH - Nod2 Signaling Adaptor Protein/*metabolism MH - STAT Transcription Factors/metabolism MH - Signal Transduction MH - Th1 Cells/immunology/metabolism MH - Th17 Cells/immunology/metabolism PMC - PMC4893688 EDAT- 2016/06/07 06:00 MHDA- 2018/04/25 06:00 PMCR- 2016/06/06 CRDT- 2016/06/07 06:00 PHST- 2016/03/09 00:00 [received] PHST- 2016/05/12 00:00 [accepted] PHST- 2016/06/07 06:00 [entrez] PHST- 2016/06/07 06:00 [pubmed] PHST- 2018/04/25 06:00 [medline] PHST- 2016/06/06 00:00 [pmc-release] AID - srep27263 [pii] AID - 10.1038/srep27263 [doi] PST - epublish SO - Sci Rep. 2016 Jun 6;6:27263. doi: 10.1038/srep27263.