The microbiome and cytosolic innate immune receptors

Abstract

The discovery of innate immune sensors (pattern recognition receptors, PRRs) has profoundly transformed the notion of innate immunity, in providing a mechanistic basis for host immune interactions with a wealth of environmental signals, leading to a variety of immune‐mediated outcomes including instruction and activation of the adaptive immune arm. As part of this growing understanding of host‐environmental cross talk, an intimate connection has been unveiled between innate immune sensors and signals perceived from the commensal microbiota, which may be regarded as a hub integrating a variety of environmental cues. Among cytosolic PRRs impacting on host homeostasis by interacting with the commensal microbiota are nucleotide‐binding domain, leucine‐rich repeat‐containing protein receptors (NLRs), together with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)–like receptors (ALRs). NLR sensors have been a particular focus of research, and some NLRs have emerged as key orchestrators of inflammatory responses and host homeostasis. Some NLRs achieve this through the formation of cytoplasmic multiprotein complexes termed inflammasomes. More recently discovered PRRs include retinoic acid‐inducible gene‐I (RIG‐I)–like receptors (RLRs), cyclic GMP‐AMP synthase (cGAS), and STING. In the present review, they summarize recent advancements in knowledge on structure and function of cytosolic PRRs and their roles in host‐microbiota cross talk and immune surveillance. In addition, we discuss their relevance for human health and disease and future therapeutic applications involving modulation of their activation and signaling.

Cationic Nanostructures for the Treatment of Inflammatory Bone Loss

“…1 In periodontitis, microbial in ammatory insults and abnormal host-microbiota interactions inappropriately and continuously activate the immune system, leading to in ammatory bone loss. 2,3 This proin ammatory immune response is initiated by toll-like receptors (TLRs) and other pattern-recognition receptors that detect and respond to pathogen-, damage-, and microbe-associated molecular patterns (PAMPs, DAMPs, and MAMPs). 4 One type of molecular pattern that contributes to periodontitis is cell-free DNA (cfDNA).…”

Intracellular innate immune receptors: Life inside the cell

“…15 Liwinski et al discuss how the cytosolic innate immune receptors are involved in shaping host-commensal interactions, with an emphasis on the physiological outcomes of these interactions. 58 The authors also discuss the challenges that exist in designing and executing experiments aimed at dissecting the microbiome-PRR relationship. 58 Van der Made et al, the authors discuss these immunodeficiencies and the mutations responsible, focusing on the rational basis for drug therapy and emphasizing the new hope being found in the management of these diseases as our knowledge of innate immunity grows.…”

“…58 The authors also discuss the challenges that exist in designing and executing experiments aimed at dissecting the microbiome-PRR relationship. 58 Van der Made et al, the authors discuss these immunodeficiencies and the mutations responsible, focusing on the rational basis for drug therapy and emphasizing the new hope being found in the management of these diseases as our knowledge of innate immunity grows. 60 The use of personalized medicine, with custom-tailored treatment plans informed by genetics and patient-specific molecular information, has a high likelihood of success for these patients.…”

Gastrointestinal epithelial innate immunity—regionalization and organoids as new model

“…The interaction between the gut microbiota as well as ingested pathogens and epithelial cells is mediated by pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)–like receptors (NLRs) and other cytosolic receptors (Fig. 2 , reviewed in [ 7 , 11 ]). These PRRs play a key role in recognizing microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs).…”

“…In addition to the classical PRRs, further sensors of bacterial activities, such as alpha-kinase 1 (ALPK1) have recently been discovered [ 17 – 19 ]. Inflammasomes, cytoplasmic complexes composed of NLR proteins, recognize additional molecular patterns, such as bacterial metabolites (reviewed in [ 7 , 9 ]).

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