Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2024

Journal

Frontiers in Cellular and Infection Microbiology

DOI

10.3389/fcimb.2024.1479801

PMID

39760094

PMCID

PMC11695292

PubMedCentral® Posted Date

12-20-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, of which idiopathic pulmonary fibrosis (IPF) is the most devastating pathologic form. Idiopathic pulmonary fibrosis pathogenesis leads to loss of lung function and eventual death in 50% of patients, making it the leading cause of ILD-associated mortality worldwide. Persistent and subclinical microbial infections are implicated in the acute exacerbation of chronic lung diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, and microbial infections as major causes for the progression and exacerbation of IPF, the role of persistent microbial infections in the pathogenesis of IPF remains unclear. In this review, we have focused on the role of persistent microbial infections, including viral, bacterial, and fungal infections, and their mechanisms of action in the pathogenesis of IPF. In particular, the mechanisms and pathogenesis of the Gram-negative bacteria Non-typeable Haemophilus influenzae (NTHi) in ILDs are discussed, along with growing evidence of its role in IPF, given its unique ability to establish persistent intracellular infections by leveraging its non-capsulated nature to evade host defenses. While antibiotic treatments are presumably beneficial to target the extracellular, interstitial, and systemic burden of pathogens, their effects are significantly reduced in combating pathogens that reside in the intracellular compartments. The review also includes recent clinical trials, which center on combinatorial treatments involving antimicrobials and immunosuppressants, along with antifibrotic drugs that help mitigate disease progression in IPF patients. Finally, future directions focus on mRNA-based therapeutics, given their demonstrated effectiveness across a wide range of clinical applications and feasibility in targeting intracellular pathogens.

Keywords

Animals, Humans, Haemophilus Infections, Haemophilus influenzae, Idiopathic Pulmonary Fibrosis, Persistent Infection, interstitial lung diseases (ILD), persistent microbial infection, idiopathic pulmonary fibrosis (IPF), non-typeable-Haemophilus influenzae (NTHi), clinical studies in IPF, mRNA-based therapeutics targeting intracellular pathogens

Published Open-Access

yes

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