Work

Early-life viral infection generates pathological tissue-resident memory cells that contribute to asthma-like disease

Year: 2026

Type: article

Abstract: Viral lower respiratory tract infections are common early in life and are associated with long-term development of asthma, a chronic condition defined by reversible airflow obstruction secondary to inflammation. Understanding the immunological mechanism connecting these two pathologies observed early in life becomes imperative to guide therapeutic measures. To investigate this connection, neonatal (days 4-6) or adult mice were infected with human metapneumovirus (HMPV) followed by a secondary HMPV infection 6 weeks later. Mice initially infected as neonates demonstrated increased mucus production, eosinophil recruitment, airway hyperresponsiveness, and Th2 T cell differentiation after rechallenge compared with adult mice rechallenged with HMPV. Neonatal HMPV infection led to formation of Th2 clonally expanded tissue-resident memory (TRM) T cells that were absent after adult HMPV. FTY720-mediated disruption of lymphocyte circulation demonstrated that TRMs contributed to pathology. Local depletion of lung CD4+ T cells and JAK2 inhibition mitigated pathology. These findings suggest TRMs uniquely generated after early-life viral infection can contribute to Th2-driven asthma pathology.

Source: JCI Insight

DOI: 10.1172/jci.insight.198712