Gone but not forgotten: lung infection history shapes future respiratory immunity

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Abstract

After respiratory infection, the lung does not simply return to the prior baseline but adopts a new distinct post-infection steady state involving durable imprints that can shape tissue responses to subsequent challenges. This review introduces the concept of lung tissue memory, whereby prior infection leaves long-term changes across immune and structural compartments, with consequences for tissue repair and disease severity during later, antigenically distinct challenges. Pre-existing and newly emerging cell populations establish networks of cell-cell crosstalk that can initiate and maintain altered cellular states. We discuss to what degree these persistent adaptations reflect shifts in cellular composition, cell-intrinsic reprogramming, changes in inflammatory tone and altered tissue niches. Finally, we propose that infection-experienced models provide a more translationally relevant framework to understand immune networks operating in the lung during infection in humans, and we present how a better understanding of tissue memory informs therapeutic strategies and improved design of antigen-specific and more broadly protective mucosal vaccines.