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Felix Ellett1,2,3, Nazli I Kacamak4,5, Carla R Alvarez4,5
1Department of Surgery, Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
Abstract:
Recent studies uncovered that Fusobacterium nucleatum (Fn), a common, opportunistic bacterium in the oral cavity, is associated with a growing number of systemic diseases, ranging from colon cancer to Alzheimer's disease. However, the pathological mechanisms responsible for this association are still poorly understood. Here, we leverage recent technological advances to study the interactions between Fn and neutrophils. We show that Fn survives within human neutrophils after phagocytosis. Using in vitro microfluidic devices, we determine that human neutrophils can protect and transport Fn over large distances. Moreover, we validate these observations in vivo by showing that neutrophils disseminate Fn using a zebrafish model. Our data support the emerging hypothesis that bacterial dissemination by neutrophils is a mechanistic link between oral and systemic diseases. Furthermore, our results may ultimately lead to therapeutic approaches that target specific host-bacteria interactions, including the dissemination process.
Insights
Fusobacterium nucleatum (Fn) survives inside human neutrophils, which then transport the bacteria. This neutrophil-mediated bacterial dissemination may link oral bacteria to systemic diseases like colon cancer.
Area of Science:
- Microbiology
- Immunology
- Pathogen-host interactions
Background:
- Fusobacterium nucleatum (Fn), an oral bacterium, is increasingly linked to systemic diseases, including colon cancer and Alzheimer's.
- The precise mechanisms driving these associations remain largely unknown.
- Understanding how Fn spreads from the oral cavity to other parts of the body is crucial.
Purpose of the Study:
- To investigate the interaction between Fusobacterium nucleatum and human neutrophils.
- To elucidate the role of neutrophils in the dissemination of Fn.
Main Methods:
- Utilized in vitro microfluidic devices to model neutrophil-bacterial interactions.
- Observed Fn survival and transport within human neutrophils post-phagocytosis.
- Validated findings in vivo using a zebrafish model to track neutrophil-mediated bacterial dissemination.
Main Results:
- Demonstrated that Fusobacterium nucleatum can survive within human neutrophils after being engulfed.
- Showed that neutrophils protect and transport Fn over significant distances in vitro.
- Confirmed in vivo that neutrophils disseminate Fn, supporting their role in spreading the bacteria.
Conclusions:
- Neutrophils play a critical role in disseminating Fusobacterium nucleatum, potentially linking oral infections to systemic diseases.
- Bacterial dissemination by neutrophils represents a key mechanism connecting oral microbiota to distant pathologies.
- These findings open avenues for therapeutic strategies targeting host-bacterial interactions, specifically the dissemination process.