Alissa Rothchild

Research focuses on the innate immune responses in the lung, studying how alveolar macrophages regulate inflammation at the airway-tissue interface.

Alveolar macrophages are tissue-resident myeloid cells, positioned at the pulmonary mucosal barrier. They are often the first cells to take up inhaled pathogens, performing a critical function as immune sentinels of the lung. In this role, alveolar macrophages must rapidly sense foreign pathogens and alert other immune cells to assist in host defense. In addition, alveolar macrophages must perform an essential homeostatic role clearing debris and dead cells from the airway without triggering excessive inflammation, yet it is unknown how alveolar macrophages balance these two seemingly opposing functions. Following aerosol transmission, alveolar macrophages are the first cells to take up Mycobacterium tuberculosis, the causative agent of Tuberculosis, and a pathogenic bacteria of global health significance. We are interested in studying alveolar macrophage innate sensing of Mycobacterium tuberculosis, how it is regulated, and the downstream events that contribute to disease outcomes.

Current Research

Role of myeloid Nrf2 expression during Mtb infection:
Our previous work found that alveolar macrophages initially respond to Mtb in a non-inflammatory manner, which is dependent on expression of the transcription factor Nrf2. Nrf2 is a master regulator for an antioxidant/oxidative stress response that regulates pathways such as glutathione metabolism and antioxidant production. Mtb-infected cells must eventually initiate innate cell recruitment and priming of the adaptive response, and the molecular basis for these events remains poorly understood. We aim to characterize how the early induction of a cell protective program by Nrf2 prevents alveolar macrophages from mounting a pro-inflammatory response to Mtb infection, delaying subsequent immune events, and leading to impaired bacterial control. Regulation of pulmonary inflammation by Nrf2 is also applicable to other respiratory infections and inflammatory conditions.

Alveolar macrophages as innate sensors and inflammatory mediators:
We are interested in how alveolar macrophages maintain dual functions within the pulmonary airway:

1. as innate sensors, recognizing Pathogen Associated Molecular Patterns (PAMPs) from direct infection, and
2. as inflammatory mediators, responding to inflammatory signals in the environment derived from other responding cells.

We aim to study how these different roles allow alveolar macrophages to maintain pulmonary homeostasis by preventing unnecessary pathology and lung damage, yet provide for sufficient immune responses to infection. Our research is  focused on understanding what signals can drive alveolar macrophages from hypo- to hyper-inflammatory states and investigating the durability of these changes.

Learn more at www.rothchildlab.com

Academic Background

• BS, Biology, Brown University, 2005
• PhD, Immunology, Harvard University, 2014
• Postdoctoral training, Seattle Children's Research Institute, 2014-2020