Suppressive role of neddylation in dendritic cells during Mycobacterium tuberculosis infection

Chadha, Attinder; Mehto, Subhash; Selvakumar, Arti; Vashishta, Mohit; Kamble, Shashank S.; Popli, Sonam; Rajagopal, Raman; Singh, Yogendra; Natarajan, Krishnamurthy

doi:10.1016/j.tube.2015.05.014

Cited by 19 publications

(34 citation statements)

References 24 publications

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“…To that end, cells were incubated with biopharmacologic inhibitors that prevent calcium release from intracellular stores or calcium influx from an external medium and inhibitors to PKC and ERK-MAPK, followed by stimulation with Pam 3 Csk 4 , in the presence or absence of Rv3529c. Recent reports from our laboratory have identified significant roles for these signaling intermediates in modulating defense responses of Mfs in M. tuberculosis [9][10][11][12]. As shown in Fig.…”

Section: Inhibition Of Ros By Rv3529c Is Dependent On Route Of Calciumentioning

confidence: 90%

“…T4 DNA ligase and ligation buffer (Thermo Fisher Scientific) were used for overnight ligation of the amplicons to the pGEMT and pET28b vector (Sigma-Aldrich). The histidine-tagged protein Rv3529c was purified with Ni-NTA agarose beads (Qiagen) followed laboratory standardized procedures [9,10]. Sequencing of the Rv3529c gene was confirmed after cloning.…”

Section: Cloning and Expression Of Rv3529cmentioning

confidence: 99%

“…Intracellular ROS levels were measured by flow cytometry, as described previously, using the redox-sensitive dye DCFH-DA [10]. THP-1-derived Mfs were stimulated with Pam 3 Csk 4 or LPS and Rv3529c for 1 h. Thirty minutes before the completion of the incubation period, cells were incubated with 10 mM DCFH-DA, while avoiding exposure to light.…”

Section: Measurement Of Oxidative Burst By Flow Cytometry and Confocamentioning

confidence: 99%

“…Rv3529c, Rv3416, and BSA were biotinylated using published protocols from the laboratory [9,10]. PMA-treated THP-1 cells were stimulated with biotinylated Rv3529c conjugated to PE-streptavidin (15 mg/ml) for 1 h. Z-stack images were collected at 1-mm intervals to score for internalization of the protein using confocal microscopy (Nikon C2).…”

Section: Biotinylation and Biotin-streptavidin Isolationmentioning

confidence: 99%

“…Having observed the proximal effects of Rv3529c on ROS generation and phosphorylation and the activation of ERK-MAPK and NF-kB pathways, we next explored its role in modulating the defense responses of Mfs, such as apoptosis. Our recent reports [9,10] have established the role of M. tuberculosis proteins in modulating apoptosis and autophagy in Mfs. We first investigated the levels of phosphatidylserine on the cell surface by Annexin V staining.…”

Section: Rv3529c Blocks Tlr2-mediated Apoptosis Of Mfsmentioning

confidence: 99%

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Suppression of Toll-like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c

Bandyopadhyay

Chadha

Gupta

et al. 2017

Journal of Leukocyte Biology

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Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β. Importantly, Rv3529c significantly inhibited TLR2-induced association of MyD88 with IRAK1 by competitively binding with IRAK1. Further, Rv3529c mediated inhibition of apoptosis and phagosome-lysosome fusion. Lastly, incubation of macrophages with Rv3529c increased bacterial burden inside macrophages. The data presented show another strategy evolved by toward immune evasion that centers on incorporating sequences in proteins that are similar to crucial proteins in the innate immune system of the host.

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Section: Inhibition Of Ros By Rv3529c Is Dependent On Route Of Calciumentioning

confidence: 90%

Section: Cloning and Expression Of Rv3529cmentioning

confidence: 99%

Section: Measurement Of Oxidative Burst By Flow Cytometry and Confocamentioning

confidence: 99%

Section: Biotinylation and Biotin-streptavidin Isolationmentioning

confidence: 99%

Section: Rv3529c Blocks Tlr2-mediated Apoptosis Of Mfsmentioning

confidence: 99%

See 3 more Smart Citations

Suppression of Toll-like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c

Bandyopadhyay

Chadha

Gupta

et al. 2017

Journal of Leukocyte Biology

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The pivotal roles of neddylation pathway in immunoregulation

Lü

Yang

2020

Immunity Inflam & Disease

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Introduction Protein neddylation, one of the most important posttranslational modifications that tagging neuronal precursor cell‐expressed developmentally downregulated protein 8 onto substrate proteins, plays fundamental roles in the process of many cellular functions. A number of studies have demonstrated the critical roles of neddylation modification in multiple pathophysiological processes, but its regulatory role in the immune system has only been finitely unveiled. Methods In this review, the latest advances in the field of neddylation modification in regulating the immune responses are succinctly discussed. Results Neddylation modification acts as a crucial modulator of innate immune cells (neutrophils, macrophages, and dendritic cells) and lymphocytes. Dysregulation of neddylation alters characteristics and functions of those cells due to abnormal degradation of key signaling molecules involved in immunoregulation. Furthermore, the ectopic immune responses caused by the abnormal neddylation play pivotal roles in a variety of immune‐related diseases, such as infection, inflammation, and cancer. Conclusions The pivotal roles of neddylation pathway in immunoregulation are attracted more and more attention, which may provide new insights into the pathogenesis of a variety of immune‐related diseases and help to indicate new therapeutic targets and potential treatment strategies.

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Interrelation of Ca2+ and PE_PGRS proteins during Mycobacterium tuberculosis pathogenesis

Meena

2019

J Biosci

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Suppressive role of neddylation in dendritic cells during Mycobacterium tuberculosis infection

Cited by 19 publications

References 24 publications

Suppression of Toll-like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c

Suppression of Toll-like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c

The pivotal roles of neddylation pathway in immunoregulation

Interrelation of Ca2+ and PE_PGRS proteins during Mycobacterium tuberculosis pathogenesis

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