Early apoptosis of monocytes induced by Helicobacter pylori infection through multiple pathways
Ying Zhang1, Hui Sun1, Huilin Zhao1
1School of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, China.
Abstract:
Only a small percentage of people infected with Helicobacter pylori (H. pylori) will develop overt chronic gastric diseases. To understand the pathological mechanism, the action of H. pylori on monocyte apoptosis was detected. H. pylori co-culturing with peripheral blood monocytes, THP-1 or U937 cells result in early apoptosis at 6, 12, and 24 h after infection. The phosphorylated Bad and JNK were increased, and Bcl-2 was declined at 6, 12, and 24 h in peripheral blood monocytes after H. pylori infection. The phosphorylated Akt was augmented at 6 and 12 h post-infection. A slow apoptotic response was induced by H. pylori via Bad and Bcl-2 regulators, activated caspase-8 and caspase-9, and JNK at 24 h in THP-1 cells. Meanwhile, only Bad and JNK were involved in regulating U937 cells apoptosis at 24 h after infection. These results supported a novel mechanism of H. pylori escaping from monocytes by upregulation of early apoptosis and inhibition of late apoptosis. The differences among the three cells may reveal why H. pylori-derived disease occurs in relatively few people and provide a pathological mechanism whereby a treatment for H. pylori-derived disease may be developed.
Insights
Helicobacter pylori (H. pylori) infection induces early monocyte apoptosis, a mechanism for immune evasion. This study reveals how H. pylori manipulates cell death pathways, potentially explaining why few infected individuals develop gastric disease.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Helicobacter pylori (H. pylori) infection is common, but only a small fraction of infected individuals develop chronic gastric diseases.
- The precise pathological mechanisms underlying H. pylori-induced gastric pathology remain incompletely understood.
- Investigating H. pylori's interaction with immune cells, specifically monocytes, is crucial for understanding disease development.
Purpose of the Study:
- To elucidate the pathological mechanisms of H. pylori infection by examining its effect on monocyte apoptosis.
- To identify the specific molecular pathways involved in H. pylori-induced monocyte apoptosis.
- To explore potential reasons for the low incidence of H. pylori-related gastric diseases.
Main Methods:
- Co-culturing H. pylori with human peripheral blood monocytes, THP-1, and U937 cell lines.
- Assessing early and late apoptosis at 6, 12, and 24 hours post-infection using flow cytometry and molecular markers.
- Analyzing the expression levels of key apoptosis-related proteins, including phosphorylated Bad, JNK, Bcl-2, and Akt, as well as activated caspases.
Main Results:
- H. pylori infection induced early apoptosis in peripheral blood monocytes, THP-1, and U937 cells at various time points.
- Infection led to increased phosphorylated Bad and JNK, and decreased Bcl-2 in peripheral blood monocytes.
- H. pylori modulated apoptotic pathways differently across cell types, involving Akt in early stages and Bad, Bcl-2, caspases, and JNK in later stages in THP-1 cells, while primarily Bad and JNK in U937 cells.
Conclusions:
- H. pylori employs a novel immune evasion strategy by upregulating early monocyte apoptosis and inhibiting late apoptosis.
- Differential apoptotic responses among monocyte cell types may explain the low prevalence of H. pylori-associated gastric diseases.
- Understanding these mechanisms provides a basis for developing targeted therapies for H. pylori-derived gastric conditions.
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