Innate immune cell contribution in wood smoke induced effects to pulmonary function
Wildfires are a growing global issue, and a significant concern for public health. Each year, wildfires continue to
make headlines as tens of thousands of fires and millions of acres burn around the world. Due to the effects of
climate change, these wildfires have become more intense and longer burning. Although wildfires threaten
lives directly, and wildfire smoke affects us all—particularly as the intensity and duration of wildfires escalates
globally. exciting new preliminary data shows that individuals from a community inundated with hazardous
levels of wildfire smoke (daily average: 220.9 µg/m3 of PM2.5) for 49 days exhibited a significant decrease in
lung function at least two years after the wildfire event, with a greater effect observed in the older (>65 years)
fraction of the cohort. Moreover, we demonstrate pulmonary inflammation and airway hyperreactivity,
facilitated by cytokine mediators in our mouse model of acute wood smoke exposure. The objective of this
proposal is to determine how wildfire smoke affects components of innate immunity, macrophage subsets and
innate lymphoid cells, into generating alarmins and inflammatory mediators that result in tissue remodeling and
decreased lung function. We propose the central hypothesis that ILC2 activities are initiated by IL-33
and macrophages in response to wood smoke exposure, resulting in the production and release of
inflammatory mediators which trigger pathology. To effectively test this hypothesis, the following specific
aims will be addressed: Aim 1: Exposure to WS will result in time-, dose-, age-, and sex-dependent adverse
pulmonary effects. Aim 2: Exposure to high levels of wildfire smoke will result in alterations to innate immune
components that will promote tissue remodeling in the lungs. The proposed studies will utilize the state-of-the-
art Inhalation and Pulmonary Physiology Core facility at the University of Montana to develop a mouse model
of the community exposures.
Impact
Together, the proposed cutting-edge murine studies complementing the ongoing unique longitudinal human
studies will have a sustained and powerful impact on wildfire smoke-induced health effects and macrophage
immunobiology. The successful completion of the project will provide a significant missing link into a novel
mechanism by which the environment adversely affects respiratory health, and also provide a link to how other
environmental pollutants (e.g. cigarette smoke, diesel exhaust, particulate matter) may serve as risk factors for
diminished lung function. Lastly by understanding how macrophage subsets influence inflammatory responses
in ILC2s, therapeutic approaches can be developed with greater precision and efficacy, thereby significantly
advancing treatment options for this growing public health concern.