As a young student, Catherine Blish, MD, PhD, found herself drawn to research. This interest took her all over the world – from an outpost in Antarctica, where she studied algae and bacteria communities on sea ice, to the plant pathology laboratory at UC Davis. Today Blish runs her own laboratory at Stanford, where she investigates new methods to prevent and control infectious diseases through better understanding of human immunology.

Her recent study, published in the Proceedings of the National Academy of Sciences, examined how a pregnant woman’s immune cells respond to influenza viruses and found that pregnant women have an unusually strong immune response to the flu. The results challenge the long-held belief that pregnancy weakens the immune system.

During an interview, she discussed her journey to medicine, her interest in immunology, and the unexpected results of her latest work. 

Q: How did you first become interested in medicine?

I came to medicine from a research background. I first became involved in research as a high school student, and worked in a whole variety of labs trying different fields, including cancer research and marine biology. I even studied sea ice microbial communities at McMurdo Station in Antarctica for a little while! Eventually I settled into medicine with a specific focus in infectious diseases. 

Q: What initially drew you to infectious diseases?

I was always interested in HIV, and, to my surprise, I found that I really liked the practice of medicine. The advantage of being an HIV doctor is that you get to treat the whole patient. Clinically, I found HIV care to be very satisfactory, because I was spending a lot of time dealing with complex infections and complications, but also still having time to treat the whole patient. I remained passionate about research, and I was drawn to the complexity of the immune system. Infectious diseases tied it all together for me.

Q: When did your focus shift from HIV to immune regulation during pregnancy?

I became interested in pregnancy from my work with HIV, because pregnant women are twofold more likely to acquire the virus and the reasons aren’t really clear.

Because of this interest in immune regulation during pregnancy, I began to look at influenza, which is a really dramatic disease during pregnancy. Although there’s no convincing data that suggests pregnant women are more likely to acquire the flu, what we do know is that they do terribly once they get it. Even today, pregnant women with influenza have a five to seven fold increased risk of hospitalization.

As part of our broader look at how the immune system changes during pregnancy and how this affects viruses, we decided to look at how pregnant women respond to  the influenza vaccine as a model system to understand the pregnant immune system. We enrolled a cohort of pregnant women to study how they responded. Prior studies had focused on pregnant women’s antibody responses, but we decided to take a broader look, using fluorescence flow cytometry and CyTOF to look at natural killer (NK) cells, T cells, and other immune functions.

We’re still analyzing a lot of the more complex data, but the response of NK cells and T cells was so dramatic that we decided to go ahead and publish that finding.  

Q: Why do you think influenza causes an enhanced immune response in pregnant women?

We don’t really know. But if I had to guess, we have some data suggesting that pregnancy itself activates an intrinsic inflammatory pathway. I think there happens to be an intersection in the setting of influenza and pregnancy, where influenza happens to activate some of the same pathways that are naturally activated during pregnancy.

Q: Could these findings change the way we treat influenza in pregnant women?

If these findings are confirmed in the real world, there are some specific inflammatory pathways that we could potentially target with therapeutics. I don’t think these therapeutics would replace the current therapy, because our current therapies are great at suppressing viral replication. However, we could potentially dampen the viral replication and then add an immune modulator to decrease inflammation at the same time. We’ll be exploring that.

The most important thing to protect pregnant women is to make sure they don’t get influenza in the first place, and the best way to do that is to get the vaccine. Though the vaccine has been shown to decrease hospitalizations for both pregnant women and their babies, only 50 percent of pregnant women get the vaccine. We’d like to use this study as an opportunity to encourage women to get vaccinated. 

Q: What’s next for you and your laboratory?

There’s a lot more work to do with this research, and data analysis is ongoing.  It’s critical that we confirm this finding in larger studies and that we make sure this immune response reflects what is happening in women who are infected naturally. 

We recently received IRB approval for a study in which we’re attempting to enroll pregnant women who are naturally infected with influenza to look at their blood when they’re infected.  We hope to do two parallel studies. The domestic study will be based at Stanford. In addition, Alexander Kay, MD, is submitting an award to study this in Africa in partnership with the CDC Kenya. These samples will help confirm whether our findings really reflect what is happening in the real world.

This interview has been edited and condensed