About this Research Topic
Sepsis remains among the leading causes of mortality with over 30 million cases worldwide per year, resulting in over 6 million deaths and huge costs for society. Sepsis is defined as a life-threatening organ dysfunction caused by a deregulated host response to infection. Advances in supportive care and antimicrobial therapy have improved patient outcome. However mortality rates remain high due to several factors including (i) disease heterogeneity, (ii) host characteristics and (iii) shortcomings in early recognition and diagnosis. Therefore, there is an urgent global need to improve the prevention, recognition, diagnosis and management of sepsis. The key to improving these processes lies in acquiring in-depth knowledge of the intricate interplay between host defense, infection and pathogen virulence as well as timing and type of interventions that are most effective according to the personal characteristics of individual patients.
Increased susceptibility to sepsis has long been known for broad patient groups, including (i) neonates, (ii) infants, (iii) the elderly and (iv) immunosuppressed patients. Yet this observation fails to explain large inter-individual differences in sepsis outcomes. Recent studies have identified common and rare genetic variation that confers increased susceptibility to infection, and have led to the identification of novel primary immunodeficiencies. Links between host genetic variation and associated effect sizes on sepsis susceptibility and/or sepsis severity have also been recently uncovered. Nonetheless, the mechanisms underlying host susceptibility to infection and deregulated immune responses leading to sepsis remain poorly understood. Furthermore, biomarkers that could be used to identify and characterize these dysregulated host responses are currently lacking.
Therefore, more research, particularly using omics-based approaches, is essential to untangle the immunologic and genetic mechanisms underlying progression from infection to sepsis. Interestingly, sepsis outcome has been shown to be related to the balance between pro-inflammatory and counteracting anti-inflammatory mechanisms involved in sepsis-induced immunoparalysis. Indeed, the immune status of patients with sepsis progresses with time, and there is a critical need for accurate monitoring of associated immune dysregulation in order to (i) determine the potential benefit of immunomodulative interventions and (ii) stratify patients to be enrolled in clinical studies and for the implementation of personalized medicine.
In this Research Topic, we aim to address the key roles of the host immune system in sepsis susceptibility, presentation and outcomes. In this way, we aim to identify new avenues for healthcare intervention and to accelerate improved treatments for sepsis. Original Research, Reviews, Mini-Reviews, Perspective, Protocols, Case Report articles are welcome for submission.
We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
Keywords: Sepsis, Host susceptibility
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