Image caption: A diagram of a lung going through active pulmonary tuberculosis (TB) from an infected person. TB is responsible for the transmission of Mycobacterium tuberculosis. Vaccines that prevent active TB are urgently needed to reduce TB cases, morbidity, and mortality. Created with Biorender.com.
Overview
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and causes over a million deaths per year. A critical unmet need is a vaccine that reliably prevents active TB, the manifestation of infection that is responsible for its morbidity and Mtb transmission. A major goal of our lab is to define the key immune features unique to T cells and macrophages able to facilitate control of Mtb growth.
Research Interests
Projects in our lab focus on understanding the effect of Mtb infection on macrophages and T cell responses to infection. We are actively engaged in understanding:
- The mechanism by which Mtb limits memory CD4+ T cell activation upon infection of M2 but not M1-like macrophages, and the roles of IL-10 signaling on T cell responses
- Lung resident T cell and macrophage responses to Mtb infection
- The relationship between TCR clonotype, antigen specificity, and effector functions of CD4+ T cells that recognize and respond to Mtb-infected macrophages
- How HIV infection impacts human memory CD4+ T cell responses to Mtb prior to reduction in CD4 count
Image caption: Memory CD4+ T cells are isolated from the blood of healthy donors with latent Mtb infection (LTBI) or after vaccination. The T cell antigen receptors (TCRs) from T cells that become activated in response to Mycobacterium tuberculosis-infected autologous macrophages are sequenced to understand the TCR repertoire and determine their functions and antigen specificity. Created with Biorender.com.
Research Techniques
In the Carpenter Lab, we make use of the following techniques:
- Ex vivo co-culture of human memory T cells and autologous macrophages infected with virulent Mtb under BSL-3 conditions
- Murine aerosol infection with Mtb under BSL-3 conditions; evaluation of immune responses in lung, spleen and lymph nodes of infected animals
- High-parameter flow cytometry to assess immune cell phenotype and function
- T cell antigen receptor (TCR) sequencing to assess repertoire and antigen specificity
- Bulk and single-cell transcriptomics for gene expression profiling
- Development of human CD4+ T cell clones
- CRISPR gene editing in primary human immune cells
- Antigen screening and epitope mapping