Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

BACKGROUND: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated. OBJECTIVE: We sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection. METHODS: We studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells. RESULTS: Intranasal acetate administration induced basal upregulation of IFN-ß, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-ß and IFN-λ gene expression during RV infection. CONCLUSIONS: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection.

Thermal and pigment characterization of environmental fungi in the urban heat island of Baltimore City.

One of the major barriers of fungal infections of mammals is the inability to grow and/or survive at mammalian body temperature, typically around 37°C. This has provided mammals an advantage over fungi. However, environmental fungi may soon adapt to persist at higher temperatures, consistent with mammalian body temperature, due to thermal selection pressures imposed by climate change, global warming, and increased frequency of extreme heat events. Consequently, there is a need for more updated information about the thermal tolerance range of fungi near humans, such as in urban areas. The heat island effect suggests that cities are up to 8°C warmer than their suburban counterparts because of increased heat production, asphalt coatings and reduced greenspace among other factors, and it is more common in lower income and marginalized urban communities. Thus, urban centers are at increased risk for the emergence of heat tolerant fungi. In this study, we developed a methodology to collect and archive fungal isolates from sidewalk and soil samples in both warmer and cooler neighborhoods in Baltimore, Maryland. We demonstrate a novel methodology for fungal sample collection from sidewalks, employing the use of standardized and commercially available taffy. Analysis of fungal isolates collected from warmer neighborhoods revealed greater thermal tolerance and lower pigmentation, suggesting local adaptation to heat. Lower pigmentation in hotter areas is consistent with the notion that fungi use pigmentation to help regulate their temperature. Further, we identified the robust presence of the polyextremotolerant fungus Aureobasidium pullalans from the warmest neighborhood in Baltimore, further showing that the extreme conditions of cities can drive proliferation of extremotolerant fungi. This study develops new techniques for environmental fungal collection and provides insight on the fungal census in an urban setting that can inform future work to study how urban environments may drive stress/thermotolerance in fungi, which could alter fungal interactions with humans and impact human health.