Vankayalapati, Ramakrishna, Ph.D.
- NK cells and T regulatory cells in M. tuberculosis infection.
- Role of NK cells in vaccine induced protective immune responses.
- To study the role regulatory T cells in human M. tuberculosis infection.
Identify immunologic markers of persons at highest risk of progression of latent tuberculosis infection to tuberculosis
The immune response to any infectious agent, including M. tuberculosis, is composed of an innate immune response and an adaptive immune response. The innate response is a form of natural immunity in which the immune cells have never previously encountered the pathogen, but can nevertheless eliminate it. Innate immunity explains why some persons are naturally more resistant to certain viral or bacterial infections. In contrast, the adaptive immune response depends on the immune system’s prior contact with a pathogen or antigens (immunogenic components) of that pathogen. For example, when someone receives a vaccine against hepatitis B, this primes the immune response so that when the person is exposed to hepatitis B, a strong adaptive immune response prevents infection.
Previous studies of the immune response to M. tuberculosis by tuberculosis patients and healthy tuberculin reactors have focused on the role of T-lymphocytes, a key component of the adaptive immune response. The innate immune response, mediated primarily by lymphocytes called natural killer (NK) cells, has not been studied because it is difficult to isolate these cells and maintain them in culture. Nevertheless, there is compelling evidence that the innate immunity is important in the response to tuberculosis. Many persons who have worked with tuberculosis patients for extensive periods never develop a positive tuberculin skin test, indicating that their T-cells do not recognize M. tuberculosis, and that the innate immune response clears the infection before the adaptive immune response develops. Second, there are significant differences in susceptibility of different ethnic groups to tuberculosis infection, African-Americans being three times more likely to become infected than Whites. This suggests that genetic differences result in significant differences in the innate immune response.
Selected Papers and Abstracts:
- Bandaru A, Kamakshi P Devalraju, Paidipally P, Dhiman R, Sambasivan Venkatasubramanian, Barnes PF, Vankayalapati R, Valluri V. STAT3 regulates IL-23 receptor expression and 1L-17 production in human Mycobacterium tuberculosis infection. (European Journal of Immunology, revision).
- Dhiman R, Paidipally P, Barnes PF, Tvinnereim A, Vankayalapati R. IL-22 enhances Calgranulin A expression by human macrophages to inhibit virulent Mycobacterium tuberculosis growth (J Infect Dis, Revision).
- Dhiman R, Periyasamy S, Barnes PF, Jaiswal AG, Paidipally P, Barnes AB, Tvinnereim A, Vankayalapati R. NK cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis. J Immunol 2012;189:897-905.
- Periyasamy S, Dhiman R, Barnes PF, Paidipally P, Tvinnereim A, Bandaru A, Valluri V and Vankayalapati R. Programmed Death 1 and Cytokine Inducible SH2-containing Protein Dependent Expansion of Regulatory T Cells Upon Stimulation with Mycobacterium tuberculosis. J Infect Dis 203:1256-1263, 2011.
- Dhiman R, Bandaru A, Barnes PF, Saha S, Tvinnereim A, Nayak RC, Paidipally P, Valluri VL, Rao LV and Vankayalapati R. c-Maf-dependent growth of Mycobacterium tuberculosis in a CD14(hi) subpopulation of monocyte-derived macrophages. J Immunol 2011;186:1638-45.
- Dhiman R, Indramohan M, Barnes PF, Nayak RC, Paidipally P, Rao LVM, and Vankayalapati R. IL-22 Produced by Human NK Cells Inhibits Growth of Mycobacterium tuberculosis by Enhancing Phagolysosomal Fusion. J. Immunol 183: 6639-6645, 2009.
- Paidipally P, Periyasamy S, Barnes PF, Dhiman R, Cosman D and Vankayalapati R. NKG2D dependent IL-17 production by human T-cells in response to an intracellular pathogen infection. J. Immunol 183: 1940-1945, 2009.
- Roy S, Barnes PF, Garg A, Wu S, Cosman D and Vankayalapati R. NK cells lyse T regulatory cells that expand in response to an intracellular pathogen. J. Immunol 180: 1729-1736, 2008.
- Garg A, Barnes PF, Roy S, Quiroga MF, Wu S, García VE, Krutzik SR, Weis SE and Vankayalapati R. Mannose-capped lipoarabinomannan- and prostaglandin E2 dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection. Eur. J. Immunol. 38: 459-469, 2008.
- Garg A, Barnes P, Porgador A, Roy S, Wu S, Griffith DE, Girard WM, Rawal N, Shetty S, Vankayalapati R. Vimentin expressed on Mycobacterium tuberculosis-infected human monocytes is involved in binding to the NKp46 receptor. J. Immunol 177: 6192-6198, 2006.