Anti-viral defense by natural microbial environmental agents - this application seeks to characterize the mechanisms through which natural environmental agents from traditional amish farms protect the…

The National Institute of Allergy and Infectious Diseases awarded the University of Arizona $806,740 on August 12, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to characterize the mechanisms by which natural environmental agents from traditional Amish farms protect the lungs against rhinovirus infection and associated asthma development in children.

The research investigates how early-life exposure to cow barn environments and barn-derived substances present in Amish household dust suppress allergic asthma phenotypes and inhibit viral respiratory illness—both major asthma risk factors in childhood populations. Prior work demonstrated that airway administration of Amish house dust extracts in mice suppresses cardinal asthma features through innate immune pathways and reduces viral infection readouts even when administered before rhinovirus exposure, suggesting that natural agents in farm environments induce both rapid and prolonged antiviral responses.

Work is performed in Tucson, Arizona, with a period of performance through July 31, 2027. The award is a Project Grant, assistance type R56, providing one year of initial funding under the NIH Allergy and Infectious Diseases Research portfolio to support innovative biomedical research addressing infectious and allergic diseases.

Anti-viral defense by natural microbial environmental agents - this application seeks to characterize the mechanisms through which natural environmental agents from traditional amish farms protect the lung against rhinovirus (RV), a respiratory pathogen strongly associated with the development of asthma, one of the most common chronic diseases of childhood. Children raised on traditional farms are protected from asthma. Protection is associated with the child's early life contact with farm animals, especially cows, as illustrated by our work in U.S. Amish and hutterite farm children. These groups are similar in genetic ancestry and most asthma-associated lifestyles. However, amish children, who are intensely exposed to COW barns in utero and throughout childhood, show low asthma risk, whereas hutterite children, who live away from COW barns and are rarely exposed to them in early life, have a 4-fold higher disease prevalence. Asthma protection among the amish is due to exposure to COW barns and barn-derived substances also present in amish but not hutterite house dust: administration of amish but not hutterite house dust extracts (DE) to mice was sufficient to suppress all cardinal phenotypes of allergic asthma. Protection by amish DE requires innate immunity because IT is abrogated in MYD88/trif-deficient mice. Asthma risk is associated with allergic sensitization but also with early respiratory viral illnesses, especially those caused by RV. Therefore, asthma protection in amish children may reflect the ability of amish farm exposure to inhibit both allergic responses and viral illnesses, thus interfering with major asthma risk factors. We investigated whether amish farm exposure protects against RV infection. Airway administration of amish DE two days or even one month before RV infection strongly reduced viral infection readouts in mice. This suggested that natural agents in amish DE induce both rapid and prolonged anti-viral responses. The latter likely represent trained immunity, an innate memory that relies on epigenetic programming. RV also elicited distinct responses in immune cells from farm-exposed (amish) VS. Unexposed (hutterite) children. We hypothesize that exposure to amish but not hutterite farm dust activates innate pathways that rapidly protect against RV infection and enduringly train anti-RV responses through epigenetic priming at key loci in specific immune cell types. Leveraging a combination of mouse and human studies, we will characterize the mechanisms underlying rapid amish DE-induced protection against RV infection (aim 1) and prolonged training of anti-RV responses by amish DE (aim 2) in mice. Hutterite DES will serve as controls in these aims. Aim 3 will compare responses to RV in immune cells from farm-exposed (amish) and unexposed (hutterite) children to define transcriptional and epigenetic programs associated with protection. Because of the link between asthma and viral infections, deciphering the anti-viral properties of amish farm exposure will potentially lead to effective asthma-protective strategies. Directly comparing the effects of amish and hutterite DES on anti-viral responses will add specificity and significance to our results.