Arshad Khan, PhD
- Assistant Professor, Department of Pathology and Laboratory Medicine
(713) 500-5266 Office
- University of Texas, Health Science Center-McGovern Medical School, Houston, Texas, USA, 2015
- Biotechnology, University of Pune, National Chemical Laboratory, Pune, India, 2008
Areas of Interests
Mechanism of Persistence of Mycobacterium tuberculosis and Host defenses, Role of pattern recognition receptors in regulating innate and adaptive immune response during M. tuberculosis infection, characterization of cells involved in persistent Mycobacterium tuberculosis infection.
Our research interests are focused on understanding the metabolism and physiology of Mycobacterium tuberculosis along with the innate and adaptive immune mechanisms of the host during the persistence of this pathogen that causes TB disease. Persistent stage of M. tuberculosis not only has the ability to tolerate antibacterial drugs but also subverts the human innate immune system and acquired immunologic clearance mechanisms in order to maintain its own long term survival. Most individuals respond to infection with M. tuberculosis by mounting a strong cellular immune response that prevents active disease but does not sterilize the host. M. tuberculosis has developed strategies to persist within macrophages and dendritic cells, its major host cells, even in the face of fully developed T cell immunity. In an infected host, M. tuberculosis primarily resides within the phagosomes of macrophages or dendritic cells and is able to arrest phagosome maturation. We are interested in determining the events and immune responses that occur in the host cells after infection with M. tuberculosis.
We are investigating pattern recognition receptor (PRR) activation mediated innate defense mechanisms and antigen presentation processing events that occur in macrophages and dendritic cells during M. tuberculosis infection. Both PRR activation and antigen presentation processes during an intracellular infection are considered vital for the clearance of the pathogen since they play important role in generating innate as well as adaptive immunity. M. tuberculosis has been reported to interfere with both class I (MHC-I) and class II (MHC-II) antigen presentation capabilities of host macrophages and dendritic cells via inhibiting the TLR2 mediated immune signaling. While studying these events of antigen processing we have discovered that certain proteases are very critical in generating peptide epitopes to facilitate immune recognition of intracellular mycobacteria, via MHC Class II-dependent priming of CD4 T cells. BCG vaccine, which is used to protect against M. tuberculosis infection, has the ability to keep these proteases inactive via altering the pH of the phagosome hence affecting the antigen presentation capabilities of Antigen Presenting Cells in which the organisms reside. We have also demonstrated that co activation of certain Toll Like Receptors (TLRs) during M. tuberculosis infection could increase the antigen presentation and Th1 cytokine response by host cells, leading to the increased efficacy of BCG vaccine. Using the agonists of various PPRs we have deciphered the mechanism of autophagy dependent increased phagocytosis during M. tuberculosis infection. These insights increase our understanding of the host-pathogen relationship during M. tuberculosis infection and lay the groundwork for strategies aimed at combating TB. These findings have also led to an increased interest in developing natural and synthetic agonist of various TLRs, as potential adjuvants that can induce autophagy, to improve the efficacy of vaccine against TB.
In our further studies we are now examining immune mechanisms that are responsible for maintaining a dormant M. tuberculosis infection, and how deficiencies in the immune responses can result in reactivation of the pathogen. We are investigating various lung resident cells and their cellular processes and immune mechanisms that could be responsible for containment of M. tuberculosis infection. Identification of the protective immune response that doesn’t allow the bacterium to replicate could provide us important clue to understand the pathogenesis of this disease and help in developing better drugs and vaccines against TB.
- Arshad Khan, Christopher R. Singh, Emily Soudani, Pearl Bakhru, Sankaralingam Saikolappan, Jeffrey D. Cirillo, N. Tony Eissa, Subramanian Dhandayuthapani, and Chinnaswamy Jagannath. Autophagy enhances the efficacy of BCG vaccine. Book Chapter. Autophagy, Infection, and the Immune Response William T. Jackson (Editor), Michele Swanson (Editor) ISBN: 978-1-118-67764-3. 362 pages. February 2015, Wiley-Blackwell.
- Pearl Bakhru, Natalie Sirisaengtaksin, Emily Soudani, Seema Mukherjee, Arshad Khan, Chinnaswamy Jagannath. (2013). BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9. Cellular Immunology. 287 (1), 53-61.
- Diana L. Bonilla, Abhisek Bhattacharya, Youbao Sha, Yi Xu,Qian Xiang, Arshad Khan, Chinnaswamy Jagannath, Masaaki Komatsu, N. Tony Eissa. (2013). Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity. 39(3):537-47.
- Shamim Akhtar, Arshad Khan, Charles D Sohaskey, Chinnaswamy Jagannath and Dhiman Sarkar. (2013). Nitrite Reductase NirBD is induced and plays an important role during in vitro dormancy of Mycobacterium tuberculosis. Journal of Bacteriology. 195(20):4592.
- Arshad Khan and Dhiman Sarkar. (2012). Nitrate reduction pathways in mycobacteria and their implications during latency. Microbiology. 158: 301-307.
- Sankaralingam Saikolappan, Jaymie Estrella, Smitha J. Sasindran, Arshad Khan, Lisa Y. Armitige, Chinnaswamy Jagannath, Subramanian Dhandayuthapani (2012). The fbpA/sapM Double Knock Out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages. PLoS ONE. 7(5): e36198.
- Christopher R. Singh, Pearl Bakhru, Arshad Khan, Qing Bo Li and Chinnaswamy Jagannath. (2011). Nicastrin- a component of γ-secretase generates a peptide epitope facilitating immune recognition of intracellular mycobacteria through MHC-II dependent priming of T cells. Journal of Immunology. 187:5495-5499.
- Arshad Khan, Dhiman Sarkar. (2008). A simple whole cell based high throughput screening protocol using Mycobacterium bovis BCG for inhibitors against dormant and active tubercle bacilli. Journal of Microbiological Methods. 73: 62-68.
- Arshad Khan, Sampa Sarkar, Dhiman Sarkar. (2008). Bactericidal activity of 2-nitroimidazole against active replicating stage of Mycobacterium bovis BCG and tuberculosis with intracellular efficacy in THP-1 macrophage. International Journal of Antimicrobial Agents. 32: 40-45.
- Arshad Khan, Shamim Akhtar, Jawid Nazeer Ahmad, Dhiman Sarkar. (2008). Presence of a functional nitrate assimilation pathway in Mycobacterium smegmatis. Microbial Pathogenesis. 44:71-77.
- Arshad Khan, Dhiman Sarkar. (2006). Identification of a respiratory-type nitrate reductase and its role for survival of Mycobacterium smegmatis in Wayne model. Microbial Pathogenesis. 41:90-95.