REVIEW article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Biofilm-Mediated Immune Dysregulation in Chronic Pulmonary Diseases: Mechanisms and Clinical Implications
Provisionally accepted
- 1Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
- 2Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 3Saarland, Saarbrücken, Germany
- 4Queen Elizabeth Hospital, Hong Kong, Hong Kong, SAR China
- 5The Second People's Hospital of Lianyungang, Lianyungang, China
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Microbial biofilms are increasingly recognized as critical modulators of chronic airway inflammation and immune dysregulation in pulmonary diseases. This review summarizes current evidence on how biofilm formation and persistence alter host immune responses, contributing to the pathogenesis of chronic lung disorders. We first outline the characteristics of respiratory biofilms and the major pathogens involved. We then discuss how biofilms reshape innate and adaptive immunity—impairing pattern recognition receptor signaling, promoting neutrophil extracellular trap (NET) formation, altering macrophage polarization, and skewing T-cell differentiation. These immune alterations sustain low-grade inflammation, tissue remodeling, and immune tolerance, driving disease progression in chronic obstructive pulmonary disease, bronchiectasis, severe asthma, and even lung cancer. We further highlight emerging diagnostic biomarkers and therapeutic approaches targeting biofilm-associated immune pathways, including combined antibiofilm and immunomodulatory strategies. Finally, we identify key knowledge gaps and propose future research directions, emphasizing multi-omics approaches and personalized interventions to better define and target biofilm-driven immune dysregulation in chronic respiratory diseases.
Keywords: Airway Remodeling, Biofilm, Chronic pulmonary disease, Immune dysregulation, Inflammation
Received: 31 Oct 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Yu, Zhang, Yao, Cho and Shang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anquan Shang
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