Impact of type 2-targeted therapies on respiratory infection risk

Purpose of review To summarize the effects of type 2 (T2) cytokine–targeting therapies on respiratory infection risk in patients with allergic diseases, with a focus on the interplay between epithelial barrier restoration and immune rebalancing. Recent findings T2 inflammation, driven by IL-4, IL-13, IL-5, and IgE, disrupts epithelial integrity and impairs mucosal defenses, increasing susceptibility to infections. Biologics targeting these pathways restore barrier function and modulate immune responses, promoting Th1/Th17-mediated antimicrobial activity. Dupilumab improves epithelial integrity and Th1/Th17 activity, with post hoc analyses from QUEST and SINUS-52 showing fewer respiratory infections compared to placebo. IL-13-specific therapies (tralokinumab, lebrikizumab) reduce excessive Th2 signaling and effector T-cell transdifferentiation, supporting mucosal homeostasis and low infection rates. IL-5-targeted biologics (mepolizumab, benralizumab) decrease eosinophil-mediated tissue injury without significantly increasing respiratory infections, despite theoretical concerns regarding antiviral defense. Omalizumab enhances Th1 antiviral pathways while reducing IgE-mediated inflammation, preserving infection control. Summary T2-modulating biologics not only control allergic inflammation but also restore epithelial and immune homeostasis, contributing to maintained or reduced respiratory infection risk. These therapies represent a dual benefit of barrier repair and immune rebalancing. Further studies are warranted to evaluate long-term infection outcomes in high-risk populations.