The goal of my laboratory is to understand the regulation and control mechanisms of immune responses at barrier surfaces specifically in the respiratory tract. We are continuously exposed to the environment by filtering liters of air each minute to provide needed oxygen in exchange to carbon dioxide to our body. A unique network of pulmonary immune cell populations ensures appropriate immune responses not only against pathogens or hazardous materials but to maintain lung function and health at steady state. However, the underlying mechanisms are poorly understood. Group 2 innate lymphoid cells (ILC2s) are the major innate lymphoid immune cell population in the lungs, tissue resident and able to orchestrate innate but also adaptive immune responses. Thus, studying the regulatory processes of ILC2 effector function is key to understand immune concepts of pulmonary immunity and health.
The microbiome plays a fundamental role in shaping the immune system and is a key determinant of health and disease. Microbial components and metabolites critically regulate ILC2 responses, influencing immune homeostasis and host defense. In this project, we will investigate how distinct microbiome compositions modulate immune cell function, with a particular focus on ILC2 responses in the lung during respiratory viral infection. A unique aspect of this study is the comparison of mice harboring a conventional laboratory microbiome with those colonized by a natural, “physiological” microbiome, enabling us to assess how microbiome diversity influences immune regulation and antiviral immunity. Overall, this project integrates immunological, microbiome, and advanced imaging approaches to provide mechanistic insights into host–microbiome interactions. By uncovering microbiome-dependent mechanisms that shape antiviral immunity, this work has the potential to inform novel microbiome-based therapeutic strategies to enhance immune protection and improve outcomes in respiratory viral infections.
Aim 1: To investigate how the host microbiome shapes the immune response to respiratory viral infections. Cellular and humoral components of the immune system will be analyzed at different timepoints with a focus on ILC2s. In addition, viral titer and lung histology will be determined. The analysis will include male vs female mice to determine and define differences based on biological sex in immune cell activation and effector function.
Aim 2: To study the composition and diversity of a physiological microbiome upon infection. The microbiome regulates pulmonary health and microbial components (in)directly regulate ILC2 function. The microbial composition will be determined during infection and analyzed by culture and sequencing analysis.