Vaccine and Microbiome.
Host-pathogen relationships are characterized by the complex interplay between host defense mechanisms and attempts to circumvent these defenses by microorganisms. Macrophages and T cells play key roles in host defense in the recognition and elimination of microorganisms. Our studies and from other groups have generated an evidence that costimulatory molecules play a potential role in immmuno-suppression in leprosy patients, also a mycobacterial disease (Agrewala et al. 1998). Recently, we have also provided a novel insight into the mechanism whereby signaling through costimulatory molecules could deliver regulatory signals. We demonstrated that the delivery of costimulatory signals by antigen presenting cells (APC) not only activates T cells but may also influence the APC itself (Agrewala et al. 1994, 1998, Suvas et al. 2002). We observed that signaling of B cells through B7-2 costimulatory molecule enhanced its proliferation and production of antibodies and augmented the level of anti-apoptotic molecules and decreased the levels of pro-apoptotic molecule. In contrast, triggering through B7-1 could efficiently block the proliferation and production of antibodies by B cells and could retard their growth and favored the up-regulation of pro-apoptotic molecules.
Our current research interest is in microbial pathogenesis in diseases like tuberculosis where a coordinated cross-talk between macrophages and T cells is essential for protection and wish to explore the following problems: (i) eventhough immunity is highly efficacious in preventing disease but is extraordinarily inefficient in terminating infection; (ii) why only 5-10% of the infected individuals develop active tuberculosis and the remaining 90% impart effective immunity against the M. tuberculosis; (iii) why macrophages play a “dual role” by providing protection to host as well as survival of the bacteria; (iv) what factors make the relationship between M. tuberculosis and host immunity labile, converting infection into clinical disease; (v) what are the regulatory signals delivered by the infected macrophages to effector T cells and in return what signals are transmitted by effector T cells to macrophages. This study would provide insights not only into mechanisms of pathogenesis but may also suggest targets for therapeutic intervention.
- PLoS One. 20:2017:e0173769. [IF: 3.2]. Antibody response against PhoPefficiently discriminates among healthy individuals, tuberculosis patients andtheir contacts. Vidyarthi A, Khan N, Agnihotri T, Siddiqui KF, Nair GR, AroraA, Janmeja AK, Agrewala JN.Crit Rev Microbiol. 1:2016:1 [IF: 8.2].
- T cell exhaustion in tuberculosis:pitfalls and prospects. Khan N, Vidyarthi A, Amir M, Mushtaq K, AgrewalaJN.Front Immunol. 7:2016:529 [IF: 5.7].
- Alteration in the gut microbiotaprovokes susceptibility to tuberculosis. Khan N, Vidyarthi A, NadeemS, Negi S, Nair G, Agrewala JN.Front Immunol. 7:2016:386 [IF: 5.7].
- Stimulation through CD40 and TLR-4 is aneffective host directed therapy against Mycobacterium tuberculosis.Khan N, Pahari S, Vidyarthi A, Aqdas M, Agrewala JN.Scientific Reports. 6:2016:27263 [IF: 5.6].
- NOD-2 Signaling DifferentiatesBone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity. KhanN, Aqdas M, Vidyarthi A, Negi S, Pahari S, Agnihotri T, Agrewala JN.Scientific Reports. 2016 Apr 7;6:23917 [IF: 5.6].