# Role of Nod-like Receptors in Helicobacter pylori Infection: Insights into Innate Immune Signaling Pathways

## TL;DR

This paper reviews how Nod-like receptors help the immune system respond to Helicobacter pylori infection and influence disease outcomes.

## Contribution

The paper provides new insights into the roles of various NLRs in immune responses and disease progression during H. pylori infection.

## Key findings

- Nod1 and Nod2 activate key signaling pathways to regulate inflammation and defense against H. pylori.
- The NLRP3 inflammasome is crucial for IL-1β and IL-18 maturation in myeloid cells during infection.
- Noncanonical NLRs like NLRP6 and NLRC5 influence inflammation and gastric tumorigenesis.

## Abstract

Helicobacter pylori is a prevalent gastric pathogen that establishes chronic infection and contributes to gastritis, peptic ulcer disease, and gastric cancer. Its persistence depends on immune evasion strategies that promote sustained low-grade inflammation in the gastric mucosa. Nucleotide-binding oligomerization domain-like receptors (NLRs) are cytosolic pattern recognition receptors that play key roles in innate immune responses against H. pylori. Nod1 and Nod2 detect bacterial peptidoglycan delivered via the type IV secretion system or outer membrane vesicles, activating NF-κB, MAPK, and interferon signaling pathways that regulate inflammatory cytokine production, epithelial barrier function, autophagy, and antimicrobial defense. The NLRP3 inflammasome mediates the maturation of IL-1β and IL-18 primarily in myeloid cells, thereby shaping inflammatory and immunoregulatory responses during infection. In contrast, NLRC4 functions in a context-dependent manner in epithelial cells and is largely dispensable for myeloid IL-1β production. Emerging evidence also implicates noncanonical NLRs, including NLRP6, NLRP9, NLRP12, NLRX1, and NLRC5, in regulating inflammation, epithelial homeostasis, and gastric tumorigenesis. In addition, genetic polymorphisms in NLR genes influence host susceptibility to H. pylori-associated diseases. This review highlights the interplay between NLR signaling, bacterial virulence, and host immunity and identifies potential therapeutic targets.