Immunogenic profiling of Mycobacterium tuberculosis DosR protein Rv0569 reveals its ability to switch on Th1 based immunity

dc.contributor.author Kanaparthi, Kala Jyothi
dc.contributor.author Afroz, Sumbul
dc.contributor.author Minhas, Gillipsie
dc.contributor.author Moitra, Anurupa
dc.contributor.author Khan, Rafiq Ahmad
dc.contributor.author Medikonda, Jayashankar
dc.contributor.author Naz, Saima
dc.contributor.author Cholleti, Sai Nikhith
dc.contributor.author Banerjee, Sharmistha
dc.contributor.author Khan, Nooruddin
dc.date.accessioned 2022-03-27T01:03:32Z
dc.date.available 2022-03-27T01:03:32Z
dc.date.issued 2022-02-01
dc.description.abstract Mycobacterium tuberculosis (M.tb) is a multifaceted bacterial pathogen known to infect more than 2 billion people globally. However, a majority of the individuals (>90%) show no overt clinical symptoms of active Tuberculosis (TB) and, it is reported that M.tb in these individuals resides in the latent form. Therefore, a huge burden of latently infected population poses serious threat to the human health. Inconsistent efficacy of BCG vaccine and poor understanding of latency-associated determinants contribute to the failure of combating M.tb. The discovery of DosR as the master regulator of dormancy, opened new avenues to understand the pathophysiology of the bacterium. Though the specific functions of various DosR genes are yet to be discovered, they have been reported as potent T-cell activators and could elicit strong protective immune responses. Rv0569 is a DosR-encoded conserved hypothetical protein overexpressed during dormancy. However, it is not clearly understood how this protein modulates the host immune response. In the present study, we have demonstrated that Rv0569 has a high antigenic index and induces enhanced secretion of Th1 cytokines IL-12p40 and TNF-α as compared to Th2 cytokine IL-10 in macrophages. Mechanistically, Rv0569 induced the transcription of these pro-inflammatory signatures through the activation of NF-κB pathway. Further, immunization of mice with DosR protein Rv0569 switched the immune response towards Th1-biased cytokine pattern, characterized by the enhanced production of IFN-γ, IL-12p40, and TNF-α. Rv0569 augmented the expansion of antigen-specific IFN-γ and IL-2 producing effector CD4+and CD8+ T-cells which are hallmarks of Th1 biased protective immunity. Additionally, IgG2a/IgG1 and IgG2b/IgG1 ratio in the serum of immunized mice further confirmed the ability of Rv0569 to skew Th1 biased immune response. In conclusion, we emphasize that Rv0569 has the ability to generate signals to switch on Th1-dominated responses and further suggest that it could be a potential vaccine candidate against latent M.tb infection.
dc.identifier.citation Immunology Letters. v.242
dc.identifier.issn 01652478
dc.identifier.uri 10.1016/j.imlet.2022.01.001
dc.identifier.uri https://www.sciencedirect.com/science/article/abs/pii/S0165247822000013
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/4024
dc.subject DosR protein
dc.subject Mycobacterium tuberculosis
dc.subject Rv0569
dc.subject Th1 immunity
dc.title Immunogenic profiling of Mycobacterium tuberculosis DosR protein Rv0569 reveals its ability to switch on Th1 based immunity
dc.type Journal. Article
dspace.entity.type
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