Tuberculosis Update: Host Response, Immunotherapy, and Animal Models

Tuberculosis Update: Host Response, Immunotherapy, and Animal Models

Tuesday, June 6, 2006

The New York Academy of Sciences

Organizer: Grant Gallagher, UMDNJ

Emerging infectious diseases are those that have newly appeared in a population or those that have existed but are rapidly increasing in incidence or geographic range. Recent examples include HIV/AIDS, Lyme disease, and hepatitis C. The New York Academy of Sciences is proud to host the Emerging Infectious Diseases Discussion Group, part of our continuing lecture series. This discussion group features keynote presentations by principal investigators, along with short presentations by promising graduate students and postdocs.


5:00 - 7:30: Presentations

Joanne Flynn, University of Pittsburgh, "TNF and Tuberculosis."

Padmini Salgame, UMDNJ, "A Tale of Two Cells: Interaction of Dendritic Cells and Macrophages with Mycobacterium tuberculosis."

Anne Goldfeld, CBR Institute for Biomedical Research, "Mechanisms of TB Host Pathogen Interactions: from Community Based Care to the Bench."


Joanne Flynn, "TNF and Tuberculosis."
Mycobacterium tuberculosis, responsible for two million deaths per year, can cause both primary disease and latent infections in humans. The factors responsible for control of M. tuberculosis include T cells, macrophages, and cytokines such as IFN-g and TNF. Formation of a granuloma, which consists of a spherical collection of macrophages and lymphocytes, is essential to the process of controlling infection and is a hallmark of tuberculosis. However, the mechanisms of granuloma formation and maintenance is not well understood. TNF is a major contributor to granuloma formation, in that mice deficient in TNF or TNF receptor 1 cannot form granulomas and do not control infection. Neutralization of TNF during chronic infection in mice leads to loss of granuloma structure and the mice succumb to the infection. The use of TNF inhibitors in humans with chronic inflammatory diseases has revealed an important role for TNF in control of latent M. tuberculosis infection. We are investigating the mechanisms by which TNF is important in granuloma formation and control of infection. TNF is induced by macrophages upon M. tuberculosis infection, and this is responsible in part for the strong induction of CXCR3-and CCR5-binding chemokines in vitro and in vivo. These chemokines may be important in the migration of cells within the lungs to form the granuloma. We have also used the murine and non-human primate models of TB to investigate the mechanisms by which the different TNF inhibitors used in humans have different effects on susceptibility to tuberculosis. These tools provide an opportunity to understand better the mechanisms by which TNF orchestrates the granulomatous response and controls infection.

Padmini Salgame, "A Tale of Two Cells: Interaction of Dendritic Cells and Macrophages with Mycobacterium tuberculosis."
Mortality and morbidity caused by the pulmonary pathogen M. tuberculosis remains alarmingly high. Although much is known about the immunology of tuberculosis, the precise nature of the protective immune mechanisms against infection and disease remain ill defined. Dendritic cells and macrophages detect the presence of pathogens via their Toll-Like Receptors (TLR) and are foremost in orchestrating the host innate immune response and in regulating the subsequent host adaptive immunity. My laboratory focuses on understanding the role of dendritic cells and macrophages in host immunity to tuberculosis. Studies examining the reprogramming of the dendritic cell and macrophage transcriptome in response to M. tuberculosis infection revealed that genes involved in Th1 priming including, Interleukin (IL)-12, IL-23, B7, CD40, and CCR7 were preferentially upregulated in dendritic cells, while the chemokine CXCL10 was highly upregulated in macrophages. Consistent with