Editors' ChoiceCOPD

Flipping the kill switch

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Science Translational Medicine  21 Jun 2017:
Vol. 9, Issue 395, eaan6192
DOI: 10.1126/scitranslmed.aan6192


Alveolar macrophages display an impairment in delayed bacterial killing in chronic obstructive pulmonary disease (COPD) that may contribute to an increased susceptibility to bacterial infection.

Chronic obstructive pulmonary disease (COPD), a disease of airway inflammation and lung tissue destruction, is a leading cause of death worldwide. In healthy airways, alveolar macrophages (AMs) are relatively quiescent to avoid an inflammatory response to every antigen exposure, which is important given the constant interaction of the airways and the environment. In COPD, AM numbers are increased and produce more proinflammatory mediators, contributing to lung tissue destruction and inflammation. COPD patients are more susceptible to bacterial respiratory infections, resulting in pneumonias and COPD exacerbations that contribute greatly to morbidity and mortality. Why COPD patients display this increased susceptibility is not completely understood, but it has been shown that the ability of AMs to phagocytose bacteria is impaired in COPD.

Bewley et al. further probed the antimicrobial functionality of COPD AMs. Consistent with previous studies, they find that COPD AMs in culture produce increased mitochondrial reactive oxygen species (mROS), a response essential for microbial killing, compared with healthy AMs. They next focus on acute infection and further show that COPD AMs display an impaired delayed microbicidal response in association with a failure to enhance mROS production in response to acute pneumococcal infection. They find that Mcl-1, an anti-apoptotic protein that delays bacterial killing, is increased in COPD AMs. Furthermore, Mcl-1+ murine transgenic macrophages display impaired microbial killing and decreased mROS production in response to acute pneumococcal infection, suggesting this defect may be Mcl-1 dependent.

Even if the initial disease-causing irritant (e.g., cigarette smoke) is removed, the airways of COPD patients are plagued by chronic inflammation, bacterial colonization, and an impaired ability to fight acute infections. Understanding how this unique environment contributes to impaired defense is an essential step in determining how to better treat these patients.

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