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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Prostaglandin D2 is involved in the regulation of inflammatory response in Staphylococcus aureus-infected mice
Haixia Bao1, Zhiguo Gong2, Jiamin Zhao2
1Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease, Ministry of Agriculture, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Saihan District, 010011 Hohhot, China; Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Saihan District, 010011 Hohhot, China; Key Lab of Germplasm Innovation and Utilization of Triticeae Crop, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Saihan District, 010011 Hohhot, China.
Abstract:
Staphylococcus aureus (S. aureus) is one of the most infamous and widespread bacterial pathogens, causing a hard-to-estimate number of uncomplicated skin infections and probably hundreds of thousands to millions of more severe, invasive infections globally per year. S. aureus may also be acquired from animals, especially in the livestock industry. The interaction mechanism of host and S. aureus has significance for finding ways to against S. aureus infection and control inflammatory response of host, while the molecular biological activities after S. aureus infection, particular in inflammatory and immune cells are not fully clear. The present study aimed to explore whether pattern recognition receptors (PRRs) mediate prostaglandin D2 (PGD2) synthesis and PGD2 participates in the regulation of inflammatory response in macrophages during S. aureus infection or synthetic bacterial lipopeptide (Pam2CSK4) stimulation. PGD2 secretion level was enhanced by mice peritoneal macrophages infected with the S. aureus. The results indicated that PGD2 secretion was impaired in S. aureus infected-macrophages from toll-like receptors 2 (TLR2)-deficient and NLR pyrin domain-containing 3 (NLRP3)-deficient mice. PGD2 synthetase (hematopoietic PGD synthase, HPGDS) inhibitors could reduce the activation of macrophage mitogen-activated protein kinase (MAPK)/nuclear factor-κ-gene binding (NF-κB) signaling pathways. HPGDS inhibition impaired cytokines (TNF-α, IL-1β, IL-10 and RANTES) secretion and macrophage phagocytosis during S. aureus infection. In addition, inhibition of endogenous PGD2 synthesis was unable to affect the TLR2 and NLRP3 expression in S. aureus-infected macrophages. Taken together, macrophage PGD2 secretion after S. aureus infection depended on receptors TLR2 and NLRP3, and the induced PGD2 participated in the regulation of inflammatory response in S. aureus-infected macrophages. Interestingly, it was found that exogenous PGD2 down-regulated the cytokines secretion and had no effect on phagocytosis in the S. aureus-infected macrophages.
Insights
Staphylococcus aureus infection triggers prostaglandin D2 (PGD2) release from macrophages, mediated by Toll-like receptor 2 (TLR2) and NLRP3. This PGD2 regulates inflammatory responses and cytokine secretion during S. aureus infection.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Staphylococcus aureus (S. aureus) is a major bacterial pathogen causing numerous infections.
- Host-pathogen interactions and inflammatory responses during S. aureus infection are not fully understood.
- Pattern recognition receptors (PRRs) role in PGD2 synthesis and inflammatory regulation needs clarification.
Purpose of the Study:
- To investigate if PRRs mediate PGD2 synthesis during S. aureus infection.
- To determine PGD2's role in regulating macrophage inflammatory responses.
- To explore PGD2's involvement in S. aureus infection and Pam2CSK4 stimulation.
Main Methods:
- Infection of mouse peritoneal macrophages with S. aureus.
- Utilizing TLR2-deficient and NLRP3-deficient mice macrophages.
- Employing hematopoietic PGD synthase (HPGDS) inhibitors.
- Assessing MAPK/NF-κB signaling pathways and cytokine secretion (TNF-α, IL-1β, IL-10, RANTES).
- Measuring macrophage phagocytosis and TLR2/NLRP3 expression.
Main Results:
- S. aureus infection enhanced PGD2 secretion in macrophages.
- PGD2 secretion was impaired in TLR2- and NLRP3-deficient macrophages.
- HPGDS inhibition reduced MAPK/NF-κB activation, cytokine secretion, and phagocytosis.
- Exogenous PGD2 downregulated cytokine secretion but did not affect phagocytosis.
Conclusions:
- Macrophage PGD2 secretion during S. aureus infection is dependent on TLR2 and NLRP3.
- Induced PGD2 regulates inflammatory responses in S. aureus-infected macrophages.
- PGD2 plays a role in modulating cytokine production and inflammatory signaling pathways.
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