The answer may come from studying zebrafish. They share approximately 75% of the same genes as humans and about 80% of genes associated with all human diseases, such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes and cancer.
Like in humans, when zebrafish are fed Western diets, it triggers the development of metabolic syndrome, leading to NAFLD and systemic chronic inflammation, which is responsible for neutrophils’ dysfunctional and hyperactive response to injuries, as her lab has shown recently.
This is no small thing. The inability of neutrophils to help with healing is crucial to sustain a normal and effective immune response to trauma and infection. A dysfunctional neutrophilic response may even have played a part in the high number of deaths among many at-risk individuals during COVID who had metabolic syndrome and NAFLD.
Her latest research focus is on trauma. Traumatic injuries are a leading cause of death and disability in people between the ages of one and 46. Her lab has recently found that in a polytrauma scenario where zebrafish are challenged with concurrent injuries, neutrophils prioritize wounds in vital organs like the liver over tissues such as the skin.
Prioritization hypotheses are not new in the neutrophil field but have mostly been studied in the context of wound versus infection. “We think that traumatic injuries in different tissues might also be sensed by neutrophils differently, using mechanisms that are lost in the presence of diet-induced systemic inflammation,” added de Oliveira.
Now she and her research team are performing omics analysis and mechanistic studies to understand how neutrophils are impacted by the presence of diet-associated, systemic chronic inflammation and liver disease in order to understand how such changes impact neutrophil response toward concurrent injuries and infection.
Dr. de Oliveira’s interest in neutrophils started at the beginning of her career at the Carlota Saldanha lab at the Institute of Molecular Medicine, where she studied inflammation using murine models and ex vivo cells isolated from human blood. She quickly got hooked on neutrophils due to their amazing capacity to quickly respond to threats and regulate all the inflammatory processes.
“Initially, we had many limitations in the field, such as the short lifespan after isolation from blood, lack of good cell culture models and the need to use invasive methodologies in mice to visualize these cells in action,” said de Oliveira.
This inspired her to find a more suitable alternative, and she found the zebrafish model, which was just emerging as a new system to study human diseases.
After that, she dedicated her PhD work to help the field establish the zebrafish model as a system to study neutrophils and the mechanisms that regulate neutrophil recruitment to injury, infection and chronic skin disease.
