Title:Host Innate Immune Responses to Microbial Pathogens
Volume: 11
Issue: 2
Author(s): Julie Delaloye and Thierry Calandra
Affiliation:
Keywords:
Sepsis, innate immunity, pattern recognition receptors, Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, RIG-I-like receptors, C-type lectin receptors, cytokine
Abstract: Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response
to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced
by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding
of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune
sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of
microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike
receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick
off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules
playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory
and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming
or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the
profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of
therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations
of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis.
Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important
components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.
