The harm of fine particulate matter (PM_2.5) to public health is the focus of attention around the world. The Global Burden of Disease (GBD) Study 2015 (GBD 2015 Risk Factors Collaborators, 2016) ranked PM_2.5 as the fifth leading risk factor for death, which caused 4.2 million deaths and 103.1 million disability-adjusted life-years (DALYs) loss, representing 7.6% of total global deaths and 4.2% of global DALYs. Epidemiological studies have confirmed that exposure to PM_2.5 increases the incidence and mortality of respiratory infections. The host defense dysfunction caused by PM_2.5 exposure may be the key to the susceptibility of respiratory system infection. Thus, this review aims to assess the impact of PM_2.5 on the host defense of respiratory system. Firstly, we elaborated the epidemiological evidence that exposure to PM_2.5 increases the risk of respiratory infections. Secondly, we summarized the experimental evidence that PM_2.5 exposure increases the susceptibility of different pathogens (including bacteria and viruses) in respiratory system. Furthermore, here we discussed the underlying host defense mechanisms by which PM_2.5 exposure increases the risk of respiratory infections as well as future perspectives.

Interleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

Pulmonary fibrosis is the end stage of a broad range of heterogeneous interstitial lung diseases and more than 200 factors contribute to it. In recent years, the relationship between virus infection and pulmonary fibrosis is getting more and more attention, especially after the outbreak of SARS-CoV-2 in 2019, however, the mechanisms underlying the virus-induced pulmonary fibrosis are not fully understood. Here, we review the relationship between pulmonary fibrosis and several viruses such as Human T-cell leukemia virus (HTLV), Human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein–Barr virus (EBV), Murine γ-herpesvirus 68 (MHV-68), Influenza virus, Avian influenza virus, Middle East Respiratory Syndrome (MERS)-CoV, Severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 as well as the mechanisms underlying the virus infection induced pulmonary fibrosis. This may shed new light on the potential targets for anti-fibrotic therapy to treat pulmonary fibrosis induced by viruses including SARS-CoV-2.

Pathological tissue remodeling is closely associated with the occurrence and aggravation of various diseases. A Disintegrin And Metalloproteinases (ADAM), as well as A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS), belong to zinc-dependent metalloproteinase superfamily, are involved in a range of pathological states, including cancer metastasis, inflammatory disorders, respiratory diseases and cardiovascular diseases. Mounting studies suggest that ADAM and ADAMTS proteases contribute to the development of tissue remodeling in various diseases, mainly through the regulation of cell proliferation, apoptosis, migration and extracellular matrix remodeling. This review focuses on the roles of ADAM and ADAMTS proteinases in diseases with pathological tissue remodeling, with particular emphasis on the molecular mechanisms through which ADAM and ADAMTS proteins mediate tissue remodeling. Some of these reported proteinases have defined protective or contributing roles in indicated diseases, while their underlying regulation is obscure. Future studies are warranted to better understand the catalytic and non-catalytic functions of ADAM and ADAMTS proteins, as well as to evaluate the efficacy of targeting these proteases in pathological tissue remodeling.

Pulmonary fibrosis, a kind of terminal pathological changes in the lung, is caused by aberrant wound healing, deposition of extracellular matrix (ECM), and eventually replacement of lung parenchyma by ECM. Pulmonary fibrosis induced by acute lung injury and some diseases is reversible under treatment. While idiopathic pulmonary fibrosis is persistent and irreversible even after treatment. Currently, the pathogenesis of irreversible pulmonary fibrosis is not fully elucidated. The known factors associated with the development of irreversible fibrosis include apoptosis resistance of (myo)fibroblasts, dysfunction of pulmonary vessel, cell mitochondria and autophagy, aberrant epithelia hyperplasia and lipid metabolism disorder. In this review, other than a brief introduction of reversible pulmonary fibrosis, we focus on the underlying pathogenesis of irreversible pulmonary fibrosis from the above aspects as well as preclinical disease models, and also suggest directions for future studies.

Increased apoptosis of alveolar epithelial cells is a prominent feature of pulmonary fibrosis. Macrophage efferocytosis, phagocytosis of apoptotic cells by macrophages, is crucial for maintaining tissue homeostasis. Expression of Mer tyrosine kinase (MERTK, an important recognition receptor in efferocytosis) in macrophages is thought to be associated with fibrosis. However, how macrophage MERTK affects pulmonary fibrosis and whether it depends on efferocytosis are not yet clear. Here, we found elevated MERTK expression in lung macrophages from IPF patients and mice with bleomycin-induced pulmonary fibrosis. In vitro experiments showed that macrophages overexpressing MERTK exhibit profibrotic effects and that macrophage efferocytosis abrogates the profibrotic effect of MERTK by downregulating MERTK, forming a negative regulatory loop. In pulmonary fibrosis, this negative regulation is defective, and MERTK mainly exhibits profibrotic effects. Our study reveals a previously unsuspected profibrotic effect of elevated macrophage MERTK in pulmonary fibrosis and defective regulation of efferocytosis function as a result of that elevation, suggesting that targeting MERTK in macrophages may help to attenuate pulmonary fibrosis.