Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection

• Published in: Scientific reports Vol. 9; no. 1; p. 7030
• Main Authors: Mejías-Luque, Raquel, Lozano-Pope, Ivonne, Wanisch, Andreas, Heikenwälder, Matthias, Gerhard, Markus, Obonyo, Marygorret
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.05.2019; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/21; 14/63; 38/77; 38/90; 631/250/256/2515; 631/67/1504/1829; 64/60; 82/51; Animals; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Carcinogenesis; CD3 antigen; Cell activation; Chemokine CXCL9 - genetics; Chemokine CXCL9 - metabolism; Epithelium; Gene expression; Genetic transformation; Helicobacter; Helicobacter felis; Helicobacter Infections - metabolism; Helicobacter Infections - pathology; Humanities and Social Sciences; Infections; Inflammation; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lymphocytes; Lymphotoxin; Male; Mice, Inbred C57BL; Mice, Mutant Strains; multidisciplinary; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; NF-κB protein; Pathology; Phenotypes; Science; Science (multidisciplinary); Signal Transduction; Stat3 protein; STAT3 Transcription Factor - metabolism; Stomach Diseases - metabolism; Stomach Diseases - microbiology; Stomach Diseases - pathology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Transcription; Tumor Necrosis Factor Ligand Superfamily Member 14 - genetics; Tumor Necrosis Factor Ligand Superfamily Member 14 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43417-x

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-κB signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response 88 (MyD88), which signals through NF-κB, led to an accelerated development of gastric pathology upon H. felis infection, but the mechanisms leading to this phenotype remained elusive. Non-canonical NF-κB signaling was shown to aggravate H. pylori -induced gastric inflammation via activation of the lymphotoxin β receptor (LTβR). In the present study, we explored whether the exacerbated pathology observed in MyD88-deficient ( Myd88 −/− ) mice was associated with aberrant activation of non-canonical NF-κB. Our results indicate that, in the absence of MyD88, H. felis infection enhances the activation of non-canonical NF-κB that is associated with increase in Cxcl9 and Icam1 gene expression and CD3 + lymphocyte recruitment. In addition, activation of signal transducer and activator of transcription 3 (STAT3) signaling was higher in Myd88 −/− compared to wild type (WT) mice, indicating a link between MyD88 deficiency and STAT3 activation in response to H. felis infection. Thereby, MyD88 deficiency results in accelerated and aggravated gastric pathology induced by Helicobacter through activation of non-canonical NF-κB.