Abstract
Lung fibrosis is characterised by the accumulation of extracellular matrix within the lung and is secondary to both known and unknown aetiologies. This accumulation of scar tissue limits gas exchange causing respiratory insufficiency. The pathogenesis of lung fibrosis is poorly understood, but immunologic‐based treatments have been largely ineffective. Despite this, accumulating evidence suggests that innate immune cells and receptors play important modulatory roles in the initiation and propagation of the disease. Paradoxically, while innate immune signalling may be important for the pathogenesis of fibrosis, there is also evidence to suggest that innate immune function against pathogens may be impaired, leading to dysregulated and/or impaired host defence. This review summarises the evidence for this pathologic two‐way street, highlights new concepts of pathogenesis and recommends future directions for research emphasis.
Highlights
The complicated interplay between respiratory pathogens and innate immunity in the fibrotic lung is extremely understudied
Summary and Recommendations for Future Research In this review, we summarize the known contributions of the innate immune system to fibrotic progression, highlighting the importance of PMNs and macrophages in driving disease in three unique models of fibrogenesis
We discuss the direct contributions of PMNs and macrophages in both lung injury and driving fibroblast proliferation and ECM production to mediate aberrant wound repair
Summary
The complicated interplay between respiratory pathogens and innate immunity in the fibrotic lung is extremely understudied. There is a body of literature that clearly supports the important role of innate immune cells in stimulating tissue injury and fibrogenesis, but it seems that innate immune cells residing in a fibrotic microenvironment may be less equipped to fight off pulmonary infection. We speculate that this two-way signaling may be another mechanism that promotes the progressive nature of lung fibrosis whereby innate immune cells trigger initial injury, but undergo reprogramming within the fibrotic niche that impairs host defense, allowing for infections or alterations to the microbiota that further damage and scar the lung.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
