Vankayalapati, Ramakrishna, Ph.D.

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Contact: krishna.vankayalapati@uthct.edu

Research Interest:

• TUBERCULOSIS
• Study the role of NK cells in human M. tuberculosis infection.

Current Projects:

1. To determine the mechanisms by which NK cells lyse M. tuberculosis-infected macrophages.
2. To study the role regulatory T cells in M. tuberculosis infection.

Lay Summary:
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:

• Garg A, Barnes PF, Roy S, Quiroga MF, Wu S, García VE, Krutzik SR, Weis SE, 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.
• Roy S, Barnes PF, Garg A, Wu S, Cosman , 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, Porgador A, Roy S, Wu S, Nanda JS, 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. 2006 Nov 1;177(9):6192-8.
• Vankayalapati R, Garg A, Porgador A, Griffith D, Klucar P , Safi H, Girard WM, Cosman D, Spies T, Barnes PF. Role of Natural Killer cell activating receptors and their ligands in the lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 175:4611-4617, 2005.
• Vankayalapati R, Klucar P, Wizel B, Weis SE, Shams H, Samten B, Barnes PF. NK cells regulate CD8+ T cell effector function in response to an intracellular pathogen. J Immunol. 2004 Jan 1;172(1):130-7.
• Vankayalapati R, Wizel B, Klucar P, Shams H, Samten B, Barnes PF. Serum cytokine concentrations do not parallel Mycobacterium tuberculosis induced cytokine production in human tuberculosis infection. Clin Infect Dis 36:24-28, 2003.
• Vankayalapati R, Wizel B, Weis SE, Safi H, Lakey DL, Porgador A, Samten B, Mandelboim O, Barnes PF. NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium is associated with enhanced expression of the NKp46 the activating receptor. J Immunol 168:3451-3457, 2002.
• Vankayalapati R, Wizel B, Lakey DL, Zhang Y, Barnes PF. T-cells enhance production of IL-18 by monocytes in response to an intracellular pathogen. J Immunol 166:6749-53, 2001.
• Vankayalapati R, Wizel B, Samten B, Griffith DE, Shams H, Galland MR, von Reyn CF, Girard WM, Wallace RJ Jr, Barnes PF. Cytokine profile in immunocompetent persons infected with Mycobacterium avium intracellulare. J Infect Dis 183:478-484, 2001.
• Vankayalapati R, Wizel B, Weis SE, Samten B, Girard WM, Barnes PF. Production of IL-18 in human tuberculosis. J Infect Dis 182:234-239, 2000.