Defining microbe-induced immune alterations precluding allergic airway eosinophilia

The National Institute of Allergy and Infectious Diseases awarded the Regents of the University of Michigan $100,228 on December 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct research on microbe-induced immune alterations that protect against allergic airway eosinophilia.

The research tests the hypothesis that inhalation exposure to Streptococcus pneumoniae confers protection against allergic airway eosinophilia—excessive eosinophil recruitment to airways that causes tissue damage and airway remodeling in asthma. Aim 1 will determine whether this protection results from IL-10 production by regulatory T cells formed during bacterial exposure. Aim 2 will determine whether protection occurs through enriched conventional dendritic cell activity during allergen encounter. The studies employ genetically engineered mouse lines, pneumococcal and asthma murine models, spectral flow cytometry, and single cell RNA sequencing. Findings will identify immune pathways targetable for next-generation asthma prevention and treatment strategies.

Work is performed at the University of Michigan in Ann Arbor, Michigan, with performance completion on June 30, 2029. This is a Project Grant, the standard assistance type for investigator-initiated biomedical research under the Allergy and Infectious Diseases Research program.

Abstract

Asthma is an inflammatory disorder of the respiratory tract triggered in response to inhalation of stimuli like allergens. IT is the most common chronic disease in children worldwide, making IT a major public health concern. A hallmark feature of asthma is the excessive eosinophil recruitment to the airways (referred to as allergic airway eosinophilia) which inflicts tissue damage, airway wall remodeling, and reduced gas exchange in the affected lungs. The hygiene hypothesis posits that exposure to commensal microbes may educate our immune system and direct IT away from development of allergies and asthma. Relevant to this, our preliminary data also suggests that inhalation experience with the frequent human nasopharynx-colonizing bacteria streptococcus pneumoniae (SPN) confers protection against allergic airway eosinophilia. How such inhaled microbial experience may mechanistically preclude allergic airway eosinophilia, however, remains unclear. In this proposal we will test the hypothesis that SPN experience protects against allergic airway eosinophilia by potentiating a treg- and a CDC1- dependent immunoregulatory axis; to be tested as part of aims 1 and 2 respectively. Aim 1 will determine whether inhaled SPN experience is protective due to the production of IL-10 by regulatory T cells (TREGS) formed during bacterial encounter, and aim 2 will determine whether SPN confers protection through the activity of an enriched CDC1 pool during allergen encounter. These studies will be accomplished using novel genetically engineered mouse lines, human relevant murine models of pneumococcal experience and asthma, spectral flow cytometry, and single cell RNA sequencing. Findings from these innovative studies will delineate pathways that may be exploited as targets for next-generation preventative and treatment strategies against asthma. What is more, this proposal will also support the applicant in scientific, professional, technical, career, and personal development through guidance by an expert mentoring team and dissertation committee, use of state-of-the-art experimental techniques, enrollment in a tailored course curriculum, engagement in workshops and seminars, and engagement in an array of science communication and mentorship opportunities. The university of michigan boasts elite academic training; connections and collaborations with experts in the fields of immunology, microbiology, pulmonology, and allergy; and cutting-edge facilities to achieve the proposed aims. Completion of this proposal will additionally support the applicant's thorough and rigorous training in creative experimental design, microbiological and immunological techniques, and data interpretation and presentation that will ensure her future success as an independent researcher and principal investigator.