Dr. Rothchild Receives Grant from the National Institute of Health/National Institute of Allergy and Infectious Diseases

Alissa Rothchild, PhD

Alissa Rothchild, an Assistant Professor in the Department of Veterinary and Animal Sciences, has received a two-year $400,000 grant from the National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) to study the early innate immune response to Mycobacterium tuberculosis infection. The grant will support research in the Rothchild lab to study how the initial pulmonary response to infection by alveolar macrophages is regulated by the transcription factor Nrf2. 

Mycobacterium tuberculosis is the causative agent of Tuberculosis (TB), a disease that kills nearly 1.5 million people each year and is one of the leading causes of death by an infectious disease globally. Mycobacterium tuberculosis is transmitted by aerosol and immune cells called alveolar macrophages in the lower respiratory tract of the lung are the first to take up bacteria. In addition to being important for lung homeostasis and maintaining airway clearance, alveolar macrophages are critical for pathogen sensing and initiating the host response that will recruit other immune cells into the lung.

Work by Dr. Rothchild and colleagues previously showed that alveolar macrophages initially respond to Mycobacterium tuberculosis by mounting a cell-protective program, rather than a pro-inflammatory one, driven by the transcription factor Nrf2. The goal of the project is to develop diverse tools to modulate alveolar macrophage Nrf2 expression to define how Nrf2 impacts the timing and quality of the early immune events during infection. The project will test the hypothesis that early Nrf2 expression is detrimental to host control by delaying and dampening the innate immune response. By developing new tools and reagents to study Nrf2 regulation of macrophage function, the Rothchild lab hopes to gain insight into the early events of Mtb infection in the lung and to evaluate the potential of Nrf2 as a future target for host-directed therapy. This grant, combined with generous enabling support from the Institute for Applied Life Sciences (IALS), provides the Rothchild lab with the critical resources needed to tackle the difficult problem of characterizing an effective host immune response against Mycobacterium tuberculosis.