Dr. Chinnaswamy Jagannath
The University of Texas Health Science Center at Houston
Department of Pathology and Laboratory Medicine
- Vaccines for tuberculosis
- TLR signaling and adjuvants
- Th1 immunity and T cells
- Dendritic cells and macrophages-pathogen survival
The major focus of my laboratory is on vaccine development for tuberculosis. Tuberculosis is the leading cause of death due to infections in the world today and we are working on newer strategies to develop vaccines. We developed a novel gene knockout vaccine from Mycobacterium tuberculosis (Mtb) that protects mice better than BCG (Infection& Immunity, 2000, 2004). We propose to develop this ultimately into a candidate vaccine for humans. Although BCG is used a vaccine against tuberculosis in man, it does not offer long term protection. Parameters for long term immunity are uncertain. However, a key defect in development of better vaccine effect is that both BCG and wild type Mtb inhibit phagosome maturation, lysosomal degradation and processing of antigens through MHC pathway so that effective T cell responses are probably not induced. We have therefore developed novel hypotheses and mechanisms to address this issue.
We are investigating the ability of candidate Mtb vaccine strains to undergo phagosome maturation within macrophages and dendritic cells (DCs) and get processed in a manner that an efficient T cell response is induced. We hope to induce long term memory by inducing the right type of effector T cell responses. Central to our efforts are our research on: a) the bactericidal function of macrophages that involves phagocyte oxidase and inducible nitric oxide synthase, b) the role of Cathepsin proteases of macrophages and DCs on mycobacterial degradation & the role of cathepsins in loading peptides to MHC complex before presentation to T cells, and c) the induction of long term immunity in mice. The role of DCs and macrophages in priming and expanding the three pathways of T-cell function (Th1, Th2 and Th3) is also a major area of thrust.
We use various strains of mice, gene knockout Mtb strains, various cell culture models and the mouse model of tuberculosis to analyze these phenomenon. We assay cellular markers using flow cytometry, analyze cellular signaling cascades with immunochemistry and PCR and analyze intracellular trafficking of pathogens with laser confocal microscopy. A tutorial in my laboratory will therefore provide an insight into the immunity mechanisms & the pathogenesis of intracellular infections as exemplified by tuberculosis.
A systems biology approach to study the phagosomal proteome modulated by mycobacterial infections. Rao PK, Singh CR, Jagannath C, Li Q.Int J Clin Exp Med. 2009 Sep 30;2(3):233-47.
Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Jagannath C, Lindsey DR, Dhandayuthapani S, Xu Y, Hunter RL Jr, Eissa NT.Nat Med. 2009 Mar;15(3):267-76. Erratum in: Nature Medicine. 2010 Jul;16(7):828.
Processing and presentation of a mycobacterial antigen 85B epitope by murine macrophages is dependent on the phagosomal acquisition of vacuolar proton ATPase and in situ activation of cathepsin D. Singh CR, Moulton RA, Armitige LY, Bidani A, Snuggs M, Dhandayuthapani S, Hunter RL, Jagannath C.J Immunol. 2006 Sep 1;177(5):3250-9.
The Delta fbpA mutant derived from Mycobacterium tuberculosis H37Rv has an enhanced susceptibility to intracellular antimicrobial oxidative mechanisms, undergoes limited phagosome maturation and activates macrophages and dendritic cells. Katti MK, Dai G, Armitige LY, Rivera Marrero C, Daniel S, Singh CR, Lindsey DR, Dhandayuthapani S, Hunter RL, Jagannath C. Cell Microbiol. 2008 Jun;10(6):1286-303.
Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT.Immunity. 2007 Jul;27(1):135-44.
Office: MSB 2.200
Ph.D. - University of Madras - 1984