Abstract

Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota. The purpose of this review is to evaluate the emerging functions of PRRs including their functional cross-talk, how they respond to mitochondrial damage, induce mitophagy or autophagy, and influence adaptive immune responses by interacting with the antigen presentation machinery. The review also summarizes some of the recent attempts to harness these pathways for therapeutic approaches in intestinal inflammation.

Highlights

  • Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens

  • The purpose of this review is to evaluate the emerging functions of PRRs including their functional cross-talk, how they respond to mitochondrial damage, induce mitophagy or autophagy, and influence adaptive immune responses by interacting with the antigen presentation machinery

  • Pattern-recognition receptor-mediated control of innate immunity has a fundamental role in both mounting immune defense and maintaining intestinal homeostasis

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Summary

Frontiers in Medicine

Activation of the innate immune system through pattern-recognition receptor (PRR) signaling plays a pivotal role in the early induction of host defense following exposure to pathogens. Loss of intestinal innate immune regulation leading aberrant immune responses has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The precise role of PRRs in gut inflammation is not well understood, but considering their role as bacterial sensors and their genetic association with IBD, they likely contribute to dysregulated immune responses to the commensal microbiota. The purpose of this review is to evaluate the emerging functions of PRRs including their functional cross-talk, how they respond to mitochondrial damage, induce mitophagy or autophagy, and influence adaptive immune responses by interacting with the antigen presentation machinery. The review summarizes some of the recent attempts to harness these pathways for therapeutic approaches in intestinal inflammation

THE INNATE IMMUNE SYSTEM AND PATHOGEN SENSING
OVERVIEW OF THE NLR FAMILY
MITOCHONDRIA PROVIDE A STRUCTURAL HUB FOR INNATE IMMUNE SIGNALING
ACTIVATION OF THE IMMUNE RESPONSE FOLLOWING MITOCHONDRIAL DAMAGE
INNATE IMMUNE MODULATION OF AUTOPHAGY
PRRs INFLUENCE ADAPTIVE IMMUNE RESPONSES
MODIFICATION OF PRR SIGNALING IN THE MANAGEMENT OF INTESTINAL INFLAMMATION
Signaling through TLRs
Polysaccharide A
Improvement Improvement
Signaling in Intestinal Inflammation
CONCLUSION
AUTHOR CONTRIBUTIONS
Full Text
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