AI Article Synopsis
- This study investigates how TLR9, activated by bacterial DNA with CpG motifs, enhances phagocytosis and autophagy in macrophages when exposed to Staphylococcus aureus.
- Researchers found that pretreatment with CpG-ODN significantly increased these immune responses, but the effects were absent in TLR9-deficient macrophages, highlighting the receptor's crucial role.
- The signaling pathways involved were identified as JNK and P38, indicating that targeting these pathways could be potential strategies for enhancing the immune response against bacterial infections.
Article Abstract
Aims: Phagocytic and autophagic responses are critical for effective host defense against bacterial infection. Bacterial DNA which contains unmethylated Cytosine-phosphate-Guanine (CpG) motifs can trigger a variety of defense mechanisms via Toll-like receptor 9 (TLR9). Here, we aimed to investigate the underlying mechanism of TLR9-mediated phagocytosis and autophagy in Staphylococcus aureus (S.aureus)-stimulated macrophages.
Main Methods: The macrophage cell line RAW264.7 or primary peritoneal macrophage was pretreated with CpG-ODN and then stimulated by S. aureus, where some of them were pretreated with SP600125 or SB203580 simultaneously. The protein expressions of TLR9, MyD88, SR-A, CD36, LC3, Beclin-1, and phosphorylated level of c-Jun N-terminal kinase (JNK), P38 and extracellular-regulated protein kinase (ERK) were detected by western blotting. The phagocytosis and LC3 punctate-structures of macrophage were observed by confocal laser scanning microscope.
Key Findings: CpG-ODN significantly amplified S. aureus-induced phagocytosis and autophagy of RAW264.7 and TLR9(+/+) primary peritoneal macrophage as compared to that of Non-CpG treated cells, while such effect was abolished in TLR9(-/-) primary peritoneal macrophages. Meanwhile, CpG-ODN significantly enhanced S. aureus-induced phosphorylation of JNK and P38 but not ERK in RAW264.7. Specific inhibition of JNK or P38 by SP600125 or SB203580, dramatically down-regulated CpG-induced phagocytosis and autophagy in S. aureus-stimulated RAW264.7 and TLR9(+/+) primary peritoneal macrophage, while they showed no further down-regulation of phagocytosis and autophagy in TLR9(-/-) primary peritoneal macrophages.
Significance: Our data indicated that CpG-ODN activates TLR9-JNK/P38 signaling to promote phagocytosis and autophagy in S. aureus-stimulated macrophages, these findings provide novel insights into how innate immune cells defend bacterial infection via TLR9.
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| http://dx.doi.org/10.1016/j.lfs.2016.07.016 | DOI Listing |
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