Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.2.3.23 (
GAS
)
957
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Helicobacter pylori
(
H. pylori
) is the strongest known risk for gastric cancer. The
H. pylori cag
type IV secretion system is an oncogenic locus that translocates peptidoglycan into host cells, where it is recognized by NOD1, an innate immune receptor. Beyond this, the role of NOD1 in
H. pylori
-induced cancer remains undefined. To address this knowledge gap, we infected two genetic models of
Nod1
deficiency with the
H. pylori cag
+
strain PMSS1: C57BL/6 mice, which rarely develop cancer, and INS-
GAS
FVB/N mice, which commonly develop cancer. Infected C57BL/6
Nod1
-/-
and INS-
GAS
Nod1
-/-
mice acutely developed more severe gastritis, and INS-
GAS
Nod1
-/-
mice developed gastric dysplasia more frequently compared with
Nod1
+/+
mice. Because
Nod1
genotype status did not alter microbial phenotypes of
in vivo-
adapted
H. pylori
, we investigated host immunologic responses.
H. pylori
infection of
Nod1
-/-
mice led to significantly increased gastric mucosal levels of Th1, Th17, and Th2 cytokines compared with
Nod1
wild-type (WT) mice. To define the role of specific innate immune cells, we quantified cytokine secretion from
H. pylori
-infected primary gastric organoids generated from WT or
Nod1
-/-
mice that were cocultured with or without WT or
Nod1
-/-
macrophages. Infection increased cytokine production from gastric epithelial cells and macrophages and elevations were significantly increased with
Nod1
deficiency. Furthermore,
H. pylori
infection altered the polarization status of
Nod1
-/-
macrophages compared with
Nod1
+/+
macrophages. Collectively, these studies demonstrate that loss of
Nod1
augments inflammatory and injury responses to
H. pylori
.
Nod1
may exert its restrictive role by altering macrophage polarization, leading to immune evasion and microbial persistence. SIGNIFICANCE: These findings suggest that manipulation of NOD1 may represent a novel strategy to prevent or treat pathologic outcomes induced by
H. pylori
infection.
...
PMID:Nod1 Imprints Inflammatory and Carcinogenic Responses toward the Gastric Pathogen
Helicobacter pylori
. 3069 58
