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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
The surreptitious survival of the emerging pathogen Staphylococcus lugdunensis within macrophages as an immune
Ronald S Flannagan1, David W Watson1, Bas G J Surewaard2,3,4
1Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
Abstract:
Staphylococcus lugdunensis is a commensal bacterium that can cause serious infection suggesting an ability to circumvent aspects of host immunity. We demonstrate here that macrophages fail to kill ingested S. lugdunensis and the bacteria persist for extended periods, without replicating, within mature LAMP-1-positive phagolysosomes. Phagocytosed S. lugdunensis also do not intoxicate host cells in contrast to Staphylococcus aureus. Optimal survival of S. lugdunensis requires O-acetylated peptidoglycan because an oatA mutant, which is more sensitive to killing by lysozyme than wild type, survived to a lesser extent in macrophages. In vitro models of macrophage infection reveal that viable intracellular S. lugdunensis bacteria can be made to grow by pharmacologic perturbation of phagosome function or by phagocyte intoxication by S. aureus toxins. Remarkably, replicating S. lugdunensis is not constrained by LAMP-1 and phosphatidylserine-positive endomembranes, which is distinct from S. aureus that replicates within phagolysosomes. In vivo, S. lugdunensis can also reside in the murine Kupffer cell where the bacteria persist without replicating and require oatA to resist killing in vivo. The intracellular environment of the macrophage represents a niche where S. lugdunensis can exist while protected from extracellular immune factors and may serve as a reservoir from which these bacteria could disseminate.
Insights
Staphylococcus lugdunensis evades macrophage killing by persisting in phagolysosomes, requiring O-acetylated peptidoglycan for survival. This intracellular niche protects the bacteria and may act as a reservoir for dissemination.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Staphylococcus lugdunensis is a commensal bacterium with pathogenic potential.
- Macrophages are key immune cells involved in bacterial clearance.
- Understanding bacterial evasion mechanisms is crucial for treating infections.
Purpose of the Study:
- To investigate the intracellular survival mechanisms of Staphylococcus lugdunensis within macrophages.
- To determine the role of O-acetylated peptidoglycan in S. lugdunensis survival.
- To compare the intracellular behavior of S. lugdunensis with Staphylococcus aureus.
Main Methods:
- In vitro macrophage infection models.
- Analysis of bacterial survival and replication within phagolysosomes (LAMP-1 positive).
- Assessment of the role of O-acetylated peptidoglycan (oatA mutant) and host cell intoxication.
Main Results:
- Macrophages fail to kill ingested S. lugdunensis, which persist in LAMP-1-positive phagolysosomes without replicating.
- Optimal survival requires O-acetylated peptidoglycan; oatA mutants show reduced survival.
- Replicating S. lugdunensis escapes phagolysosomal and endomembrane constraints, unlike S. aureus.
- In vivo, S. lugdunensis persists in murine Kupffer cells, requiring oatA for resistance.
Conclusions:
- The macrophage intracellular environment serves as a protective niche for S. lugdunensis.
- O-acetylated peptidoglycan is essential for S. lugdunensis resistance to host immunity.
- S. lugdunensis intracellular persistence may act as a reservoir for dissemination.
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