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Peptidoglycan accelerates granulopoiesis through a TLR2- and MyD88-dependent pathway
Masaya Takehara1, Soshi Seike1, Teruhisa Takagishi1
1Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Abstract:
Granulopoiesis is accelerated during Gram-negative bacterial infection through activation of toll-like receptor 4 (TLR4). In this study, we tested whether activation of TLR2 promotes granulopoiesis by using the well-known TLR2 agonist, peptidoglycan (PGN). Neutrophils in bone marrow and spleen, and plasma granulocyte colony-stimulating factor (G-CSF) were increased in mice that had received intraperitoneal PGN administration. Incorporation of BrdU into bone marrow neutrophils increased, demonstrating that PGN accelerated granulopoiesis. Treatment of bone marrow cells (BMCs) with PGN increased neutrophils in vitro and promoted the secretion of G-CSF from Ly-6G-Ly-6C+ monocytes. The accelerated granulopoiesis caused by PGN was not seen in TLR2-deficient and MyD88-deficient BMCs. Additionally, PGN induced G-CSF production in human umbilical vein endothelial cells. These findings demonstrate that PGN promotes the secretion of G-CSF from monocytes and endothelial cells, leading to the acceleration of granulopoiesis. Our results illustrate that bacterial recognition by TLR2 facilitates granulopoiesis during Gram-positive bacterial infection.
Insights
Toll-like receptor 2 (TLR2) activation by peptidoglycan (PGN) accelerates granulopoiesis. PGN stimulates granulocyte colony-stimulating factor (G-CSF) secretion from monocytes and endothelial cells, enhancing neutrophil production during bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Hematology
Background:
- Gram-negative bacterial infections accelerate granulopoiesis via toll-like receptor 4 (TLR4) activation.
- The role of toll-like receptor 2 (TLR2) in regulating granulopoiesis remains less understood.
Purpose of the Study:
- To investigate whether TLR2 activation by peptidoglycan (PGN) promotes granulopoiesis.
- To elucidate the mechanisms by which PGN influences neutrophil production.
Main Methods:
- Administration of PGN to mice and assessment of neutrophil counts and granulocyte colony-stimulating factor (G-CSF) levels.
- In vitro treatment of bone marrow cells (BMCs) with PGN.
- Analysis of PGN-induced G-CSF secretion from monocytes and endothelial cells.
- Experiments utilizing TLR2-deficient and MyD88-deficient BMCs.
Main Results:
- PGN administration increased neutrophil numbers in bone marrow and spleen, and elevated plasma G-CSF levels in mice.
- PGN treatment accelerated granulopoiesis, evidenced by increased BrdU incorporation into bone marrow neutrophils.
- In vitro, PGN increased neutrophil production and promoted G-CSF secretion from Ly-6G-Ly-6C+ monocytes.
- PGN induced G-CSF production in human umbilical vein endothelial cells.
- The PGN-induced acceleration of granulopoiesis was abrogated in TLR2-deficient and MyD88-deficient BMCs.
Conclusions:
- Peptidoglycan (PGN) activates TLR2, leading to enhanced granulopoiesis.
- PGN promotes G-CSF secretion from monocytes and endothelial cells, which drives accelerated neutrophil production.
- TLR2-mediated recognition of bacterial components facilitates granulopoiesis, particularly during Gram-positive bacterial infections.