Modulation of T Cell Activation During Mycobacterium Tuberculosis Infection
Abstract
Infections with Mycobacterium tuberculosis (Mtb) cause the severe pulmonary disease Tuberculosis (TB and are responsible for over 1.5 million deaths each year. Additionally, over 1/3 of the world's population has been exposed to infected individuals. One of the major reasons Mtb infections are so lethal is the normal host response is unable to eradicate the pathogen, leading to chronic infections in some individuals that can develop into active disease. We continue to lack effective tools to eradicate Mtb infections, including a protective vaccine, fast acting anti-infective drugs, and biomarkers that predict who will or will not progress to active TB. In most Mtb infected individuals the expansion and activation of Mtb-specific T cells is robust. With effective initial activation, why are these cells not sufficient to sterilize Mtb infections? One possibility is that although these T cells are functional, they are unable to detect Mtb within infected cells limiting their ability to control infection. Several studies suggest that Mtb can modulate T cell effector functions and evade T cells ability to detect infected cells. We reason that identifying host pathways that can reprogram infected cells to more effectively signal to T cells would be an important addition to the host-directed therapy toolbox. The overall goal of our Discovery Award is to identify targets that can be augmented in infected cells to improve adaptive immune responses against Mtb infection. Here we will focus on modulating key molecules that directly signal to T cells on infected macrophages and test whether altering their expression directly impacts T cell function and control during Mtb infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2021
- Accession Number
- AD1139944
Entities
People
- Andrew Olive
Organizations
- Michigan State University