Last winter, University of Vermont immunologist Jonathan Boyson, Ph.D. and his daughter both got the flu. She recovered in a few days, but it took him more than a week to kick the bug.

Boyson, the Roger G. Allbee Professor of Surgery, wonders why some people fend off this type of infection more easily than others.

In an effort to answer that question, his research has examined the role that genetics play in the effectiveness of a person’s immune response. A recently-published Infection and Immunity study in mice determined that individual genetic makeup influences the ability of certain white blood cells to resist the common pathogen Pseudomonas aeruginosa, a bacteria found throughout the environment that is responsible for a significant number of hospital-acquired lung infections.

That work is informing Boyson’s latest project – supported by a two-year $423,000 exploratory grant from the National Institutes of Health (NIH) – which is looking at a subset of genes that control the performance of those same cells, called NKT cells, in preventing and fighting influenza. Boyson is conducting this research as a faculty investigator in the Vermont Center for Immunobiology and Infectious Diseases, which is supported by a Centers of Biomedical Research Excellence (COBRE) grant from that National Institute of General Medical Sciences of the NIH.

In the study, some breeds of mice had poorly performing NKT cells that failed to stave off Pseudomonas, which is particularly risky for immune-compromised patients and those with weakened lungs from diseases such as cystic fibrosis. The pathogen recently has developed antibiotic resistance, making it more difficult to treat, Boyson says.

“We’re all exposed to Pseudomonas all the time, and most people who are exposed to it have no problem whatsoever,” Boyson says. “However, if it gains a foothold, it’s extremely dangerous.”

The NKT cells control another type of cells, called alveolar macrophages, which actually gobble up the infection and remove it from the body. Without functioning NKT cells, the macrophages don’t work well, either.

“We think their role is like generals in a battle,” Boyson says of NKT cells. “They are on the front lines” in the liver, intestines and lungs, he explains, and “take in a lot of information, make some decisions, and tell other cells what to do.”

All of this happens in the first few hours of the infection, so a lot rides on the ability of the NKT cells to do their job.

The Infection and Immunity study, co-authored by Matthew Wargo, Ph.D., assistant professor of microbiology and molecular genetics, and Matthew Poynter, Ph.D., associate professor of medicine and member of the Vermont Lung Center, settled a long-running controversy between two previous studies involving NKT cells and Pseudomonas . One, which caused a stir, found that mice with no NKT cells couldn’t clear the bacteria from their systems. A second study seeking to replicate those findings didn’t use the same mouse strain, so was not able to demonstrate the importance of the NKT cells. Those conflicting results had cancelled each other out – until Boyson’s study determined that the difference was linked to different mouse genetic backgrounds.

As in mice, Boyson believes, some human individuals’ NKT cells might not work as well to protect them against certain diseases.

“We know so little about what [the cells] do in humans,” he says.

The study suggests that some existing drugs might be able activate NKT cells in patients who are having trouble fighting Pseudomonas, Boyson says.

For the grant, Boyson proposed a focus on influenza, because it afflicts so many people. A previous study showed that, when NKT cells were removed from mice, they were more susceptible to the flu.

A group of genes known as SLAM genes – which are polymorphic, meaning they differ from person to person – control NKT cell function by sending a signal to those cells through a protein called SAP in order to attack the infection. With the grant, Boyson intends to breed and cross-breed mice specifically to create differences in the SLAM genetic makeup and see if that changes the mice’s vulnerability to flu.

According to Boyson, identification of genetic differences that regulate susceptibility to common pathogens like influenza in otherwise healthy individuals could have broad implications on public health.