Host innate immune responses to sepsis

Abstract

The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis.

Can we find accessible and relevant markers for sepsis outcome?

“…(2,3,(8)(9)(10) A recent study showed that SIRS criteria failed to identify 1 of 8 patients with severe sepsis, that 2 SIRS criteria do not represent a cut-off for risk and that the risk of death is increasing linearly with each additional SIRS criteria. (11) We did not find any correlation between the number of SIRS criteria and sepsis severity based on mortality.…”

Pro-Inflammatory Cytokines in Sepsis: Biological Studies and Prospects From In Silico Research

“…Mrp8 also acts as an active component of the binding of the Mrp8/14 complex to TLR-4, increasing TNF-α expression [9,23,38]. Additionally, it promotes the systemic inflammatory response by activation of the TLRs [38] and Mrp8 and Mrp14 levels are elevated in patients with sepsis [37]. It is increasingly recognized that the inflammatory response and unregulated production of cytokines play fundamental roles in the development of organs dysfunction.…”

“…They can form heterodimers, that are released in response to stress and their direct antimicrobial effect is commonly associated with phagocytosis [37]. The Mrp8/14 complexes amplify the phagocytic inflammatory response triggered by endotoxin, increasing recruitment of inflammatory cells to lesion sites.…”

Sepsis- The Dilemma Continues

“…Sepsis is a dysregulated host response to a suspected infective agent that is amplified by endogenous factors [3,4]. To date, there is no single mediator or pathway that drives the pathogenesis of sepsis but rather a multifaceted response that involves interplay between various body systems; an inflammatory/ immune response, cardiovascular, neuronal, hormonal, metabolic and coagulation [3][4][5].This interplay will ultimately contribute to either the progression to septic shock and multiorgan dysfunction or the complete walling off of the infection thus limiting its effects on the rest of the body organs.…”