Researchers described a potential new mechanism as to why patients with idiopathic pulmonary fibrosis (IPF) are at a higher risk of developing complications and dying following lung infections, as published in JCI Insight.
Lung fibrosis may have an impact on innate immune cell function in patients with IPF, which may be a major factor mediating survival, the authors said. A better understanding of this impact could help develop new treatments for this progressive fatal disease.
Methicillin-resistant Staphylococcus aureus (MRSA) is often isolated from the lungs of patients with IPF who are hospitalized, and these patients tend to have increased morbidity and mortality following bacterial infections.
To elucidate the effects of fibrotic lung injury on critical immune responses against infections, a team of researchers led by Bethany B. Moore, PhD, from the University of Michigan in Ann Arbor used a mouse model with IPF to elucidate the effect of the disease on innate immunity and bacterial infection.
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Like humans, mice with IPF who are infected with MRSA also had high morbidity and mortality compared to uninfected mice with IPF.
“We determine that fibrosis confers a defect in MRSA clearance compared to non-fibrotic mice, resulting from blunted innate immune responses,” the researchers wrote. They also showed that fibrosis inhibits intracellular killing of MRSA by neutrophils through the impaired release of the neutrophil elastase enzyme and the production of oxidative radicals.
Finally, they showed that macrophages in the lungs of mice with IPF were not able to phagocytize MRSA in the same way as those in the lungs of normal mice.
“Our study describes potentially novel impairments to antimicrobial responses upon the development of pulmonary fibrosis,” the authors concluded. “Our findings suggest a possible mechanism for why IPF patients are at greater risk of morbidity and mortality related to infection.”
Warheit-Niemi HI, Edwards SJ, SenGupta S, et al. Fibrotic lung disease inhibits innate immune responses to Staphylococcal pneumonia via impaired neutrophil and macrophage function. JCI insight. Published online January 6, 2022. doi:10.1172/jci.insight.152690