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Published on: July 28, 2015
Salmonella and S. aureus Escape From the Clearance of Macrophages via Controlling TFEB
Shanshan Rao1, Tao Xu2, Yu Xia2
1Department of Pathology, Wuhan Central Hospital, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Phagosome- and xenophagosome-lysosome systems play a critical role in the defense of pathogenic bacteria, such as Salmonella and S. aureus, in macrophages. A great part of the bacteria escapes from the digestion and can survive through some mechanisms that are still poorly understood and which require further exploration. Here we identified that Salmonella inhibited the expression and activation of TFEB to blunt the functions of lysosomes and defense of clearance by activating caspase-1. The expression and activation of TFEB were enhanced early under the infection of S. aureus, which was followed by shrinkage to weaken lysosomal functions due to the delayed activation of ERK, mTOR, and STAT3. Thus, we have identified novel escape mechanisms for Salmonella and S. aureus to deepen and strengthen our strategies fighting with pathogens.
Insights
This study reveals how Salmonella and Staphylococcus aureus evade macrophage defenses. Salmonella inhibits TFEB activation, while S. aureus initially enhances it before weakening lysosomal function, uncovering novel bacterial escape strategies.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Phagosome-lysosome pathways are crucial for clearing bacterial pathogens like Salmonella and Staphylococcus aureus within macrophages.
- Many bacteria possess poorly understood mechanisms to escape digestion and survive intracellularly.
Purpose of the Study:
- To elucidate novel bacterial escape mechanisms employed by Salmonella and Staphylococcus aureus within macrophages.
- To investigate the role of Transcription Factor EB (TFEB) and associated signaling pathways in bacterial survival.
Main Methods:
- Investigated the impact of Salmonella and S. aureus infection on TFEB expression and activation in macrophages.
- Analyzed the role of caspase-1, ERK, mTOR, and STAT3 signaling pathways in bacterial evasion.
- Compared the differential effects of Salmonella and S. aureus on lysosomal function and bacterial clearance.
Main Results:
- Salmonella was found to inhibit TFEB expression and activation by upregulating caspase-1, thereby impairing lysosomal function and bacterial clearance.
- Staphylococcus aureus initially enhanced TFEB expression and activation but subsequently weakened lysosomal functions through delayed activation of ERK, mTOR, and STAT3 signaling pathways.
- These findings highlight distinct strategies used by Salmonella and S. aureus to counteract host defense mechanisms.
Conclusions:
- Identified novel mechanisms of immune evasion for Salmonella and S. aureus involving the modulation of TFEB and lysosomal pathways.
- The study provides a deeper understanding of bacterial pathogenesis and suggests potential targets for developing enhanced anti-pathogen strategies.
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