Research Groups

Mammalian Biology: Immunology

Research Interests and Description

Staff Research Scientist: Krishnamurthy Natarajan

Research Interests

Mycobacterium tuberculosis, dendritic cells, cytokines, signal transduction, immune responses.

Description of Research

Previous work conducted by the Group has shown that many M. tb antigens induce the differentiation and maturation of DCs. However, these DCs induce suppressor responses to mycobacteria by modulating the activation of intracellular signaling molecules leading to increased bacterial burden. We have further demonstrated that these DCs express low levels of pro-inflammatory chemokines and thereby fail to recruit activated T cells. Conditioning DCs with cytokines and chemokines enhances recruitment and activates effector T cell responses that mediate killing of M. tb inside macrophages. Furthermore, adoptive transfer of these DCs into mice carrying an established M. tb infection leads to clearance of infection which is better than that obtained with drug treatment. To carry forward the above results, in the next step, we are currently characterizing immune responses by antigens enriched from infected macrophages at different times-post-infection, in both mouse and human cohorts. In addition we are also investigating M. tb mediated modulations of DC function using siRNA library approach. Together, this would give insights into the immune evasive strategies employed by M. tb towards downregulating protective responses from DCs.

Recent Publications

Salam, N., Gupta, A., Sharna, S., Pahujani, A., Sinha, R.K., Saxena, Natarajan, K. 2008. Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP10-differentiated dendritic cells. PLoS One 3, e2869

Sinha, A., Singh, A., Satchidanandam, V., Natarajan, K. 2006. Impaired generation of reactive oxygen species during differentiation of Dendritic cells (DCs) by Mycobacterium tuberculosis secretory antigen (MTSA) and subsequent activation of MTSA-DCs by mycobacteria results in increased intracellular survival. J Immunol. 177, 468-478

Latchumanan, V., Balkhi, M.Y., Sinha, A., Singh, B., Sharma, P., Natarajan, K. 2005. Regulation of immune responses to Mycobacterium tuberculosis secretory antigens by Dendritic cells. Tuberculosis 85, 377-383

Balkhi, M.Y., Sinha, A., Natarajan, K. 2004. Dominance of CD86, TGF-β and Interleukin-10 from Mycobacterium tuberculosis Secretory Antigen Activated Dendritic Cells Regulate T Helper 1 responses to Mycobacterial Antigens. J. Infect. Dis. 189, 1598-1609