Seminars in Immunopathology最新文献

Abstract

Glycoprotein 2 (GP2) is a widely distributed protein in the digestive tract, contributing to mucosal barrier maintenance, immune homeostasis, and antigen-specific immune response, while also being linked to inflammatory bowel disease (IBD) pathogenesis. This review sheds light on the extensive distribution of GP2 within the gastrointestinal tract and its intricate interplay with the immune system. Furthermore, the significance of GP2 autoantibodies in diagnosing and categorizing IBD is underscored, alongside the promising therapeutic avenues for modulating GP2 to regulate immunity and maintain mucosal balance.

Despite the rapid development of safe and effective COVID-19 vaccines and the widely recognized health and economic benefits of vaccination, there exist stark differences in vaccination rates across country income groups. While more than 70% of the population is fully vaccinated in high-income countries, vaccination rates in low-income countries are only around 30%. The paper reviews the factors behind global COVID-19 vaccine inequity and the health, social, and economic costs triggered by this inequity. The main contributors to vaccine inequity include vaccine nationalism, intellectual property rights, constraints in manufacturing capacity, poor resilience of healthcare systems, and vaccine hesitancy. Vaccine inequity has high costs, including preventable deaths and cases of illnesses in low-income countries, slow economic recovery, and large learning losses among children. Increasing vaccination rates in low-income countries is in the self-interest of higher-income countries as it may prevent the emergence of new variants and continuous disruptions to global supply chains.

The lungs serve as the primary organ for respiration, facilitating the vital exchange of gases with the bloodstream. Given their perpetual exposure to external particulates and pathogens, they possess intricate protective barriers. Cellular adhesion in the lungs is robustly maintained through tight junctions, adherens junctions, and desmosomes. Furthermore, the pulmonary system features a mucociliary clearance mechanism that synthesizes mucus and transports it to the outside. This mucus is enriched with chemical barriers like antimicrobial proteins and immunoglobulin A (IgA). Additionally, a complex immunological network comprising epithelial cells, neural cells, and immune cells plays a pivotal role in pulmonary defense. A comprehensive understanding of these protective systems offers valuable insights into potential pathologies and their therapeutic interventions.

Epithelial cells, which are non-immune cells, not only function as a physical defence barrier but also continuously monitor and eliminate aberrant epithelial cells in their vicinity. In other words, it has become evident that epithelial cells possess immune cell-like functions. In fact, recent research has revealed that epithelial cells recognise the Major Histocompatibility Complex I (MHC-I) of aberrant cells as a mechanism for surveillance. This cellular defence mechanism of epithelial cells probably detects aberrant cells more promptly than the conventional immune response, making it a novel and primary biological defence. Furthermore, there is the potential for this new immune-like biological defence mechanism to establish innovative treatment for disease prevention, leading to increasing anticipation for its future medical applications. In this review, we aim to summarise the recognition and attack mechanisms of aberrant cells by epithelial cells in mammals, with a particular focus on the field of cancer. Additionally, we discuss the potential therapeutic applications of epithelial cell-based defence against cancer, including novel prophylactic treatment methods based on molecular mechanisms.

The COVID-19 pandemic had a significant economic and health impact worldwide. It also reinforced the misperception that only viruses can pose a threat to human existence, overlooking that bacteria (e.g., plague and cholera) have severely haunted and shaped the course of human civilization. While the world is preparing for the next viral pandemic, it is again overlooking a silent one: antimicrobial resistance (AMR). This review proposes to show the impact of bacterial infections on civilization to remind the pandemic potential. The work will also discuss a few examples of how bacteria can mutate risking global spread and devastating outcomes, the effect on the global burden, and the prophylactic and therapeutic measures. Indeed, AMR is dramatically increasing and if the trend is not reversed, it has the potential to quickly turn into the most important health problem worldwide.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged late in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic that has so far claimed approximately 20 million lives. Vaccines were developed quickly, became available in the end of 2020, and had a tremendous impact on protection from SARS-CoV-2 mortality but with emerging variants the impact on morbidity was diminished. Here I review what we learned from COVID-19 from a vaccinologist's perspective.

Ischemic stroke is a leading cause of morbidity and mortality and disproportionally affects women, in part due to their higher longevity. Older women have poorer outcomes after stroke with high rates of cognitive deficits, depression, and reduced quality of life. Post-stroke inflammatory responses are also sexually dimorphic and drive differences in infarct size and recovery. Factors that influence sex-specific immune responses can be both intrinsic and extrinsic. Differences in gonadal hormone exposure, sex chromosome compliment, and environmental/social factors can drive changes in transcriptional and metabolic profiles. In addition, how these variables interact, changes across the lifespan. After the onset of ischemic injury, necrosis and apoptosis occur, which activate microglia and other glial cells within the central nervous system, promoting the release of cytokines and chemokines and neuroinflammation. Cells involved in innate and adaptive immune responses also have dual functions after stroke as they can enhance inflammation acutely, but also contribute to suppression of the inflammatory cascade and later repair. In this review, we provide an overview of the current literature on sex-specific inflammatory responses to ischemic stroke. Understanding these differences is critical to identifying therapeutic options for both men and women.

Severe loss of cerebral blood flow causes hypoxia and glucose deprivation in the brain tissue, resulting in necrotic cell death in the ischemic brain. Several endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), are extracellularly released from the dead cells to activate pattern recognition receptors (PRRs) in immune cells that infiltrate into ischemic brain tissue following the disruption of the blood-brain barrier (BBB) after stroke onset. The activated immune cells produce various inflammatory cytokines and chemokines, triggering sterile cerebral inflammation in the ischemic brain that causes further neuronal cell death. Poststroke inflammation is resolved within several days after stroke onset, and neurological functions are restored to some extent as neural repair occurs around peri-infarct neurons. Clearance of DAMPs from the injured brain is necessary for the resolution of poststroke inflammation. Neurons and glial cells also express PRRs and receive DAMP signaling. Although the role of PRRs in neural cells in the ischemic brain has not yet been clarified, the signaling pathway is likely to be contribute to stroke pathology and neural repair after ischemic stroke. This review describes the molecular dynamics, signaling pathways, and functions of DAMPs in poststroke inflammation and its resolution.

Despite years of encouraging translational research, ischemic stroke still remains as one of the highest unmet medical needs nowadays, causing a tremendous burden to health care systems worldwide. Following an ischemic insult, a complex signaling pathway emerges leading to highly interconnected thrombotic as well as neuroinflammatory signatures, the so-called thromboinflammatory cascade. Here, we thoroughly review the cell-specific and time-dependent role of different immune cell types, i.e., neutrophils, macrophages, T and B cells, as key thromboinflammatory mediators modulating the neuroinflammatory response upon stroke. Similarly, the relevance of platelets and their tight crosstalk with a variety of immune cells highlights the relevance of this cell-cell interaction during microvascular dysfunction, neovascularization, and cellular adhesion. Ultimately, we provide an up-to-date overview of therapeutic approaches mechanistically targeting thromboinflammation currently under clinical translation, especially focusing on phase I to III clinical trials.