A pathologic twoâ way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity

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 immunologicâ 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 twoâ way street, highlights new concepts of pathogenesis and recommends future directions for research emphasis.Innate immunity has been shown to promote the development of lung injury and fibrosis through a myriad of mechanisms. New information also suggests that the fibrotic milieu can impair the function of innate immune cells, leading to further infection, dysbiosis and fibrotic progression.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149765/1/cti21065.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149765/2/cti21065_am.pd