PROJECT SUMMARY/ABSTRACT
Nontuberculous mycobacteria (NTM) cause an emerging, chronic, and challenging to treat pulmonary disease
(PD) whose numbers now undeniably surpass tuberculosis cases in the United States (U.S.) and other
geographic regions globally. NTM infections are notoriously difficult and expensive to eradicate, prone to relapse
and reinfection, and refractory to current anti-mycobacterial therapies. The environmental niches of NTM also
remain largely ill-defined. This lack of knowledge contributes to the on-going frustration to understand where
these pulmonary infections are acquired. In the U.S., Hawai’i is a geographic hot spot for NTM PD. Our work in
Hawai’i revealed an abundance of respiratory important NTM including Mycobacterium abscessus subsp.
abscessus, Mycobacterium avium, and Mycobacterium chimaera in household and non-household water
biofilms and soil. A unique environmental factor that may impact NTM PD in Hawai’i is exposure to aerosol
pollutants from the Kilauea volcano, one of the most actively erupting volcanoes on Earth. Fine volcanic ash
particles can be breathed deep into the lungs causing irritation and cough. But, is it possible for volcanic ash to
also carry infectious NTM? Through our data, we show microbiological culture of viable M. abscessus, M. avium,
and M. chimaera from ash recovered during the 2018 eruption of Kilauea and also from the Kilauea environment,
supporting the possibility of volcanic ash as a newly described fomite for NTM. We demonstrate Kilauea ash is
not directly toxic to Kilauea-derived NTM and that ash exposure reduces NTM control by human macrophages.
Our project’s broad, long-term objective is to elucidate the innate immunological mechanisms used by human
lung cells in response to NTM infection and aerosol pollutants such as volcanic ash, providing implications that
extend beyond Hawai’i with millions of people worldwide living within kilometers of actively erupting volcanoes.
Herein, we leverage our unique collection of volcanic ash and NTM isolates recovered from Kilauea ash, the
Kilauea environment, and other Hawai’i and non-Hawai’i samples to test the hypothesis that Kilauea ash
exacerbates control of NTM infection by healthy lung cells through antagonizing NLRP3 inflammasome-mediated
pyroptosis defenses. In this proposal, we will: (i) Investigate the biological consequences of Kilauea ash
exposures on Kilauea NTM fitness in the absence of host cells and (ii) Determine the effect of Kilauea ash on
NLRP3 inflammasome-mediated pyroptosis in clearance of NTM using primary human alveolar macrophages
and airway epithelial cells cultured at the air-liquid interface from healthy donors, but also introduce a new 3D
apical out airway epithelial organoid culture system to study innate immune responses to Kilauea NTM and
Kilauea ash. The study’s broad application will be a reduction in the biological uncertainties surrounding how
exposure to specific environmental respiratory pollutants of global significance such as volcanic ash influences
NTM survival inside and outside of healthy human lung cells, while simultaneously informing risk assessments
and therapeutic interventions in response to respiratory infections and volcanic ash exposures.
