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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Pathogenic Neisseria hitchhike on the uropod of human neutrophils
Niklas Söderholm1, Katarina Vielfort, Kjell Hultenby
1Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
Abstract:
Polymorphonuclear neutrophils (PMNs) are important components of the human innate immune system and are rapidly recruited at the site of bacterial infection. Despite the effective phagocytic activity of PMNs, Neisseria gonorrhoeae infections are characterized by high survival within PMNs. We reveal a novel type IV pilus-mediated adherence of pathogenic Neisseria to the uropod (the rear) of polarized PMNs. The direct pilus-uropod interaction was visualized by scanning electron microscopy and total internal reflection fluorescence (TIRF) microscopy. We showed that N. meningitidis adhesion to the PMN uropod depended on both pilus-associated proteins PilC1 and PilC2, while N. gonorrhoeae adhesion did not. Bacterial adhesion elicited accumulation of the complement regulator CD46, but not I-domain-containing integrins, beneath the adherent bacterial microcolony. Electrographs and live-cell imaging of PMNs suggested that bacterial adherence to the uropod is followed by internalization into PMNs via the uropod. We also present data showing that pathogenic Neisseria can hitchhike on PMNs to hide from their phagocytic activity as well as to facilitate the spread of the pathogen through the epithelial cell layer.
Insights
Pathogenic Neisseria bacteria adhere to polymorphonuclear neutrophils (PMNs) using type IV pili. This interaction allows bacteria to evade immune cells and spread infections.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are key innate immune cells crucial for combating bacterial infections.
- Neisseria gonorrhoeae exhibits remarkable survival within PMNs, posing a significant clinical challenge.
Purpose of the Study:
- To investigate the novel mechanism of pathogenic Neisseria adherence to PMNs.
- To elucidate the role of type IV pili in this interaction and subsequent bacterial survival.
Main Methods:
- Scanning electron microscopy (SEM) and total internal reflection fluorescence (TIRF) microscopy were used to visualize bacterial-PMN interactions.
- Live-cell imaging and electrography were employed to study bacterial internalization and PMN responses.
Main Results:
- Pathogenic Neisseria utilizes type IV pili to adhere to the uropod of polarized PMNs.
- Bacterial adhesion triggers the accumulation of the complement regulator CD46.
- Neisseria meningitidis adhesion involves PilC1 and PilC2 proteins, unlike N. gonorrhoeae.
- Internalization into PMNs via the uropod and subsequent immune evasion were observed.
Conclusions:
- Pathogenic Neisseria employs a unique pilus-mediated adherence strategy to the PMN uropod for immune evasion.
- This mechanism facilitates bacterial survival and dissemination, highlighting a novel aspect of Neisseria pathogenesis.
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