Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Trained immunity and macrophage reprogramming in allergic disorders

"Practice is the hardest part of learning,and training is the essence of transformation."Ann Voskamp,One Thousand Gifts:A Dare to Live Fully Right Where YouAre Early-life exposure to environmental allergens and viral infections can lead to trained immunity and macrophage polarization resulting in an augmented type 2 immune response in allergic disorders.However,the detailed mechanism is unknown.

Early-life EV-A71 infection augments allergen-induced airway inflammation in asthma through trained macrophage immunity

Virus-induced asthma is prevalent among children,but its underlying mechanisms are unclear.Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma.Nonetheless,the relationship between systemic virus infections,such as enterovirus infection,and the ensuing effects on allergic asthma development is unknown.Early-life enterovirus infection was correlated with higher risks of allergic diseases in children.Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period.Bone marrow-derived macrophages(BMDMs)from recovered EV-A71-infected mice showed sustained innate immune memory(trained immunity)that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites.Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice,which was inhibited by 2-deoxy-D-glucose(2-DG)pretreatment,suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.