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Review | Open Access

Interplay between bacteria and pulmonary immune system in respiratory infections

Jiaqi Li1,2,#Letong Yang1,2,#Xiwen Qin3Min Zhao1( )Shuo Wang1,2( )
Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
University of Chinese Academy of Sciences, Beijing, China
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Missouri, USA

#These authors contributed equally to this work

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Highlights

• Respiratory bacterial pathogens are recognized by pattern recognition receptors (PRRs) and activate innate immune cells.

• Pathogen clearance by immune responses is counterbalanced by collateral inflammatory tissue injury.

• Pulmonary commensal bacteria critically regulate immune homeostasis in the mucosa.

• Prebiotic-based therapies demonstrate potential to recalibrate the immune balance and combat bacterial infections.

Abstract

The local immune system of the lungs is essential for the defense against pathogens, and respiratory bacterial infections remain a major cause of mortality in patients with lower respiratory tract diseases. However, the precise mechanisms underlying immune–pathogen interactions and the modulatory roles of commensal bacteria remain incompletely understood. This review discusses the mechanisms of immune recognition and inflammatory responses during bacterial respiratory bacterial infections, highlighting the importance of pattern recognition receptors, including toll-like receptors, nucleotide oligomerization domain-like receptors, and C-type lectin receptors in detecting pathogens and triggering immune signaling pathways. We also explore how commensal bacteria influence the respiratory immune microenvironment and discuss the complex interplay among pathogenic bacteria, commensals, and the host pulmonary immune system. This analysis provides a theoretical foundation for the development of targeted therapeutics against bacterial respiratory infections.

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hLife
Pages 3-15

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Cite this article:
Li J, Yang L, Qin X, et al. Interplay between bacteria and pulmonary immune system in respiratory infections. hLife, 2026, 4(1): 3-15. https://doi.org/10.1016/j.hlife.2025.09.006

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Received: 17 January 2025
Revised: 29 August 2025
Accepted: 15 September 2025
Published: 01 January 2026
© 2025 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).