Dr. Vankayalapati received his PhD degree from Osmania University, India. He joined the University of Texas Health Science Center at Tyler in 1999 after completion of his first postdoctoral fellowship at the Toronto General Hospital, University of Toronto. He was promoted to Instructor in 2001, Assistant Professor in 2004, Associate Professor in 2007 and Professor in 2013. He is currently serving as Chair, Department of Pulmonary Immunology and Margaret E. Byers Cain Chair for Tuberculosis Research.
The major focus of our laboratory is to study immune responses to Mycobacterium. tuberculosis (M. tuberculosis) infection. 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.
The major on-going studies in our laboratory are:
- Role of natural killer (NK) cells in the immune response to M. tuberculosis infection. NK cells are major innate immune cell population. NK cells are known to contribute to immunity against viral infections and tumors. Limited information is available about on their role in M. tuberculosis infection. During the last decade, we found that human NK cells contributes to effective immunity against M. tuberculosis infection. Our current and future goal is to determine the mechanisms through which NK cells enhance immune responses to M. tuberculosis infection.
- To study the role of regulatory T-cells in M. tuberculosis infection. T cells (components of adaptive immunity) are crucial for protective immunity against M. tuberculosis and other intracellular pathogens, in part through production of a soluble factor called IFN-γ. However, uncontrolled T-cell responses can cause tissue damage, which can be reduced by a subpopulation of T-cells called regulatory CD4+ T-cells (Tregs) that express CD25 and FoxP3. Recently we made a surprising observation that a subpopulation of M. tuberculosis-expanded human CD4+CD25+FoxP3+ cells produce a factor called Rho GDP dissociation inhibitor (D4GDI), which inhibits M. tuberculosis growth. Currently we are determining the role of CD4+CD25+Foxp3+Tregs and D4GDI in M. tuberculosis infection, using human and mouse models.
- Identify immunologic markers of persons at highest risk of progression of latent tuberculosis infection to tuberculosis. Tuberculosis (TB) kills 1.3 million persons annually. According to World Health Organization estimation, one-third of the world’s population have latent tuberculosis infection (LTBI). Most of the LTBI+ individuals remain well, but 10% eventually develop TB. Identification of persons with LTBI who are at greatly increased risk for development of TB would be a significant breakthrough that would allow public health resources to be focused on high-risk individuals to prevent future development of TB. Severe immunosuppression due to HIV infection and treatment with corticosteroids and anti-TNF blockers markedly increase the risk of progression of LTBI to active TB, but limited information is available about other immune mechanisms that favor reactivation of TB. Among persons who are not clinically immunocompromised, no biomarkers are known to identify persons at increased risk for progression of LTBI to TB. We are following a large cohort of patients with LTBI in collaboration with a Dr. Vijaya Valluri (LEPRA society – Blue Peter Public Health & Research Centre in Hyderabad, India), we will determine if development of TB is preceded by specific changes in cellular markers of monocytes, NK cells and Tregs.
Vankayalapati R, Wizel B, Weis SE, Safi H, Lakey DL, Porgador A, Samten B, Mandelboim O and 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, Klucar P, Wizel B, Weis SE, Shams H, Samten B and Barnes PF. Natural Killer (NK) cells regulate CD8+ T- cell mediated effector function in response to intracellular infection. J Immunol 172:130-137, 2004.
Vankayalapati R, Garg A, Porgador A, Griffith D, Klucar P, Safi H, Girard WM, Cosman D, Spies T and 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.
Garg A, Barnes P, Porgador A, Roy S, Wu S, Griffith DE, Girard WM, Rawal N, Shetty S, and Vankayalapati R. Vimentin expressed on Mycobacterium tuberculosis-infected human monocytes is involved in binding to the NKp46 receptor. J. Immunol 177: 6192-6198, 2006.
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.
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.
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.
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.
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.
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, Periyasamy S, Barnes PF, Jaiswal AG, Paidipally P, Barnes AB, Tvinnereim A and Vankayalapati R. NK cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis. J Immunol 2012;189:897-905.
Dhiman R, Paidipally P, Barnes PF, Tvinnereim A and Vankayalapati R. IL-22 enhances Calgranulin A expression by human macrophages to inhibit virulent Mycobacterium tuberculosis growth. J Infect Dis 2014; 209: 578-87.
Bandaru A, Kamakshi P Devalraju, Paidipally P, Dhiman R, Sambasivan Venkatasubramanian, Barnes PF, Vankayalapati R and Valluri V. STAT3 regulates IL-23 receptor expression and 1L-17 production in human Mycobacterium tuberculosis infection. Eur J Immunol. 2014 Mar 19.
Venkatasubramanian S, Dhiman R, Paidipally P, Cheekatla SS, Tripathi D, Welch E, Tvinnereim AR, Jones B, Theodorescu D, Barnes PF, Vankayalapati R. A Rho GDP dissociation inhibitor produced by T-cells inhibits growth of Mycobacterium tuberculosis. PLoS Pathog. 2015 Feb;11(2): e1004617.
- National Institutes of Health
- CRDF global
- Potts Memorial Foundation
- Cain Foundation for Infectious Disease Research
- Department of Pulmonary Immunology