Fusobacterium nucleatum dissemination by neutrophils

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.

Keywords:

• Fusobacterium nucleatum
• Neutrophil
• Phagocytosis
• Microfluidic
• Zebrafish
• Trojan Horse

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statement

Microinjection of larvae was approved by the Massachusetts General Hospital Subcommittee on Research Animal Care under Protocol 2011N000127. This protocol adheres to the federal Health Research Extension Act and the Public Health Service Policy on the Humane Care and Use of Laboratory Animals, overseen by the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

We acknowledge funding from the National Institutes of Health (GM092804 to DI and R01AG062496 to AK) and the Shriners Hospitals for Children (71010-BOS-22 to DI).