Research Topic

Long-term Consequences of Sepsis and Severe Trauma on Innate and Adaptive Immunity

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Inflammation is one component of the complex biological response to various stimuli, such as small molecular motifs found within pathogens, biomolecules released from damaged cells, or other irritants, and is considered to be a protective mechanism. Irrespective of the underlying cause (infection or sterile ...

Inflammation is one component of the complex biological response to various stimuli, such as small molecular motifs found within pathogens, biomolecules released from damaged cells, or other irritants, and is considered to be a protective mechanism. Irrespective of the underlying cause (infection or sterile tissue damage) or extent (localized or systemic), one critical function of the immune response is to clear the source of inflammation, remove damaged/dead cells, and support wound healing and tissue regeneration, which collectively enables the host to re-establish homeostasis.

In recent years, growing evidence suggests that the host immune system does not completely return to its starting point following an inflammatory immune response, but rather exhibits long-lasting alterations that can substantially enhance (e.g., “trained immunity”) or impair cellular responsiveness (e.g., “endotoxin tolerance”) to subsequent challenges. The prevailing concept is that the more severe the encountered host inflammatory response, the more pronounced cellular and molecular alterations imprint is observed. From available epidemiological studies, long-term impairment of quality-of-life and increased healthcare usage/cost due to secondary complications have been reported for survivors of critical illness.

Sepsis and severe trauma incorporate an exaggerated and systemic immune response followed by prolonged immunosuppression. The pathogenesis of sepsis is complex and variable, depending on the pathogen load and virulence, host comorbidity, genetic and epigenetic factors, environment, and the amount of time passed after the onset of the infection, with distinct phases of the immunological responses defined at local and systemic levels.

There remains a fair degree of uncertainty about the system-wide consequences of septic or traumatic event on the host, as a large body of evidence has been derived from ex vivo experiments. In particular, there is a paucity of information that clearly defines how long the observed quantitative and qualitative alterations in the immune system endure and how these changes are propagated over time and through cellular turnover. Moreover, while the concept of sepsis-induced immunosuppression (immunoparalysis) has been framed, it remains to be determined to what extent an observed change(s) in any immune cell type representation or function represents a global maladaptive or beneficial adaption - a notion with important implications related to the overall health and well-being of sepsis survivors.

The scope of this Research Topic is to compile Original Research articles and Reviews on the aftermath of sterile and infection-associated inflammation, with the intent to close the current gaps in our knowledge regarding the cellular and molecular mechanisms that govern long-term impairments in the ability of the immune system to function properly.

We welcome the submission of Original Research articles and Reviews, that cover, but are not limited to, the following topics:

· Cellular and molecular mechanisms that govern the prolonged sepsis-induced immunoparalysis or improved cellular responsivity
· Epigenetic and transcriptional reprogramming of immune cells after severe inflammation and/or infection
· Host-level analysis of susceptibility and predisposition to secondary (opportunistic) infection, mediated by changes of the immune system upon initial activation
· Analysis of alterations in tissue-resident innate and adaptive immune cell subsets following sterile and/ or infection-associated inflammation
· Inter- and transgenerational epigenetic inheritance of changes in the immune system after parental inflammation and/or infection


Keywords: inflammation, infection, immune tolerance, trained immunity, susceptibility


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