Status: Funded - Open
Blair Armistead, PhD, MPH
BACKGROUND: Respiratory tract infection is a leading cause of illness, hospitalization, and death in children under one year of age, with the highest risk among infants who live in low resource settings and/or have comorbidities. Breastfeeding in the first year of life is associated with reduced risk of respiratory infection. Although the immunological benefits of breastmilk have been attributed to immunoglobulins and antimicrobial compounds, human milk is also rich in memory T cells, which have unknown origin and function. GAP: This research will elucidate a respiratory-mammary axis of immunity that drives the establishment of memory T cells in the lactating breast. HYPOTHESIS: I hypothesize that memory T cells in both the lactating breast and the maternal respiratory tract originate from a common population of precursor cells and share adaptations for barrier-specific function (Fig. 1). METHODS: I will perform 1) single cell RNA sequencing (scRNAseq) with paired T cell receptor (TCR) sequencing on maternal nasal mucosal cells (NBC), breastmilk cells (BMC), and peripheral blood mononuclear cells (PBMC) to examine whether breastmilk and respiratory tract T cells are derived from a common population; and 2) high-parameter flow cytometry on maternal NMC, BMC, and PBMC to compare distribution and phenotype of T cell memory subsets in the lactating breast and respiratory mucosa. RESULTS: Pending. IMPACT: Discerning the relationship between T cells in the lactating breast and maternal respiratory mucosa will lend critical insight into the potential for the lactating breast to respond to respiratory infection in the mother-infant dyad and has potential to inform maternal vaccination strategies to maximize protection in the nursing infant.