An interview with Assoc Prof. Xin Luo on “Regulation of neonatal immunoglobulin A (IgA) production by the maternal microbiota”

This content is part of the Research in Practice in Immunology series of interviews with scientists, focusing on how their research work can have impact on medical practice. Click here to follow 'Research in Practice in Immunology' - for free - on Researcher for more great interviews.

Can you introduce yourself and then where you work and share your research interests?

My name is Xin Luo. I'm an associate professor of immunology at the department of biomedical sciences and pathobiology at Virginia Tech. My research interests are microbiota, autoimmunity, neonatal immunity, and nutritional immunology. There are two main directions in my laboratory, one dissects the roles of diet and gut microbiota in the pathogenesis of lupus. The other is a better understanding of how microbiota shapes neonatal immune system development. This second direction is what we're talking about today.

Can you tell us about your research paper and why this topic is so important?

This was by accident that we stepped into this field. In 2015, a very productive student of mine, who is now Dr. Qinghui Mu, made an interesting observation that a normal mouse pup, when nursed by an immunodeficient mother, had more IgA or immunoglobulin A in its blood than one nursed by a normal mother. IgA is an important antibody that protects our mucosal surfaces, such as those in the intestinal tract, from infections. A higher level of IgA in the blood suggests more protection, but it's counterintuitive to think that immunodeficient mothers, such as one infected with HIV, will provide more protection to her baby than a mom with a normal immune system. When we tested the ability of the extra neonatal IgA to bind common enteric pathogens such as Salmonella, nothing happened, suggesting that this IgA may not be protective. As my postdoc advisor, Nobel Laureate, David Baltimore once said, everything happens for a reason in biology. Therefore, my alternative hypothesis says that this extra IgA will cause autoimmunity in a neonate when it becomes an adult. We already have some evidence suggesting this hypothesis. Although we're still in the process of understanding why this occurs, we have made significant progress in analyzing how this occurrs. It turns out that the milk microbiota of the immunodeficient mother contains a bacterium called Lactobacillus reuteri, that by itself can induce neonatal IgA. This work, which is now published on PNAS, took six years to complete. Interestingly, some strains of Lactobacillus reuteri, are considered healthy and used as probiotics in infant formulas. We have found that different strains of the bacteria are completely different in their effects on the immune system. Finding out which strains are good, and which are bad, will significantly improve our understanding of the probiotic, and guide formula designs to benefit infant health. That is why it's important for the field. 

What is the impact of the research and what is the connection between your research in clinical settings?

It's too early to connect this research to medical practice. As mentioned earlier, some strains of Lactobacillus reuteri are used as probiotics, and we know that this bacterium can induce IgA in neonates. However, we do not know whether Lactobacillus reuteri-induced IgA is beneficial or detrimental. We have shown that this IgA cannot bind to enteric pathogens suggesting a lack of protective effect. But how about other pathogens, for which there is likelihood that it is going to be protective. We also have the alternative hypothesis that this IgA is an early indication of self-reactivity or autoimmunity, especially for those genetically predisposed to develop autoimmunity. We are working on these questions and hope to provide a definite answer soon. We also need to translate this research from mice to humans. While we have been using human-derived Lactobacillus reuteri strains to facilitate translation, the mouse immune system is very different from the human immune system. Down the road, we plan to use models that are more clinically relevant, such as the humanized mouse, or rhesus macaque. Once we know whether this extra neonatal IgA is good or bad in the preclinical models, we can move on to test more hypotheses clinically.  

My next step is a little different from therapeutically or clinically. Personally, I'm more interested in dissecting the underlying mechanisms as a scientist. How does Lactobacillus reuteri induce neonatal IgA? Why can some strains do so? Why can't others? And is this extra IgA good or bad? This is a project that I'm very passionate about. We are going to certainly do this in the next few years. I have reached out to paediatricians close by to try to see if we can collect faecal samples from infants and analyze their microbiota with a focus on specific strains of Lactobacillus reuteri. I'm interested in infants born to mothers who have an autoimmune disease. I hope that the analysis of Lactobacillus reuteri would be able to predict whether the infant will be able to develop autoimmunity in the future.

Is there anything that would you like to add?

It's a big passion of mine to understand how we can better infant health. We stepped into the project by accident, and it has become a fruitful direction that we plan to work on for years to come.

You can read and discover Assoc Prof. Xin Luo’s research here.

Regulation of neonatal immunoglobulin A (IgA) production by the maternal microbiota is published in PNAS

Photo Credits: Virginia Tech 

Disclaimer: This is a transcript of a video conversation. You can listen to the recording on Researcher.