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.

Warm up, cool down, and tearing apart in NK cell memory

“Memories warm you up from the inside.But they also tear you apart.”―Haruki Murakami,Kafka on the Shore.One of the characteristics of the human immune system,in addition to the recognition of nonself pathogens and the tolerance of self-antigens,is its memory response to previously encountered pathogens and the mounting of a stronger,faster secondary response against these same antigens.A long-held paradigm in immunologic study in vertebrates is that immune memory is restricted to the adaptive immune response via memory T and B cells,which possess two distinct features:specificity(recognizing pathogen antigen fragments through surface receptors)and longevity(proliferation and long-term survival after the first encounter).1–3 Unlike adaptive immunity,the innate immune system exhibits a rapid response against pathogens and transforming cells without a previous encounter,and this response depends on a series of default genes and proteins expressed on cell surfaces and in the cytoplasm that recognize the pathogen-associated molecular patterns(PAMPs)of pathogens.Therefore,it was surprising to find several models of pathogen infections in invertebrates,including insects,worms,and jawless fish,that lack fully developed adaptive immunity but possess the features of antigen specificity and longevity likely involving phagocytic cells that can“recall”prior infection with limited specificity.In fact,immune memory has recently been described in vertebrate myeloid lineages,4 in which epigenetic changes are proposed to occur in macrophages previously stimulated through pattern recognition receptors.

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.

Disease tolerance to infection: the immune defense strategy of mitoribosome targeting

“In the practice of tolerance,one’s enemy is the best teacher”.-Sayings of Buddhism.To survive an infection,two evolutionarily conserved defense strategies are required for infected host survival.One strategy in volves acquiri ng resista nee by reduci ng pathogen load via pathoge n recog nition,signaling tran sducti on pathways,and effector mechanisms.Another strategy involves increasing disease tolerance by eliciting tissue damage control mechanisms,which adjust the metabolic output of host tissue in response to different forms of stress and damage.Hence,in recent research,disease tolera nee is regarded as an in here nt comp onent of immunity,which does not exert a direct impact on pathogens but is essential to limit the health and fitness costs of infection;however,its molecular bases remain poorly understood.

Global Pediatric Pulmonology Alliance(GPPA)proposal for COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)remains a global epidemic.As of August 18,2021,the number of reported cases has exceeded 207 million globally,with more than 4.3 million deaths.COVID-19 has brought devastating losses to human society.The overall crude mortality rate is 1-3%.Although pediatric deaths from COVID-19 are rare,they do occur,as over 9,000 children have died from COVID-19 globally to date[1].With the gradual and broad application of COVID-19 vaccines around the world,the rising proportion of cases among children and unvaccinated young adults demands attention.According to World Health Organization surveillance data.

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.