Dr. Hongbing Yu, a research associate in the Jacobson and B. Vallance Research Teams, is working on basic science that could help explain why some kids get intestinal infections and others do not. His work could also lead to the development of novel treatments for inflammatory bowel disease.
Dr. Yu and his team recently published “Vasoactive Intestinal Peptide Promotes Host Defense Against Enteric Pathogens by Modulating the Recruitment of Group 3 Innate Lymphoid Cells” in PNAS.
We spoke to Dr. Yu about this research.
What are the key findings of this research?
We uncovered neuroimmune interactions in the gut that play a huge role in host defense against intestinal infections such as Escherichia coli (E. coli). We studied a neuropeptide called vasoactive intestinal peptide (VIP) that is secreted by both neurons and immune cells. We found that VIP promotes the recruitment to the intestine of important immune cells called group 3 innate lymphoid cells (ILC3s). ILC3s control the formation of immune tissues in the intestine, regulate inflammation and play key roles in intestinal defense. For example, ILC3s are critical for defense against infection in newborns when their adaptive immunity is still developing.
What happens if an organism does not have VIP?
When you don’t have VIP, a lot of immune cells will be missing from the gut. This is a big deal because more than 80 per cent of immune cells are located in the gut! So when these cells are missing and the immune system is not able to do its job, the host is not protected from a variety of pathogens. There will also be increased risk of developing inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis.
We looked at a mouse model for this research, and found that mice lacking VIP or its receptor were highly susceptible to severe Citrobacter rodentium (C. rodentium) infection, which is similar to E. coli infection in humans. Replacing the ILC3s or their products in these mice partially or fully restored their resistance to infection.
How do your findings matter when it comes to treatment of gastrointestinal infections in kids?
When a child has a bacterial intestinal infection, in a lot of cases the standard treatment is antibiotics to kill the bacteria. We are proposing a different target — instead of killing bacteria, a better choice may be to increase production of VIP.
Once we’re able to identify patients who have a lack of VIP, possibly through genetic testing, we may be able to essentially resupply the patient with this neuropeptide or treat them with a recombinant protein called interleukin-22 (IL-22). IL-22 is typically supplied by ILC3s, but if the person is lacking these immune cells, they will not produce this protein. IL-22 is an important cytokine that helps maintain the lining of the gut and defends against pathogens. There’s real promise for IL-22 treatment if it can be adjusted for this particular application in humans.
How do your findings relate to the microbiome?
VIP can actually control microbiota composition in the gut. If you don’t have this neuropeptide, the microbiota is essentially “messed up.” In other words, without VIP the composition of microorganisms is disrupted, which we know is related to the development of a variety of medical conditions, including inflammatory bowel disease.
The research team is co-led by Dr. Kevan Jacobson and Dr. Bruce Vallance. In addition to Dr. Hongbing Yu, the Vancouver team includes:
- Dr. Hyungjun Yang
- Dr. Joannie Allaire
- Caixia Ma
- Franziska Graef
- Qiaochu Liang
- Dr. Else Bosman
- Dr. Gregor Reid
- Dr. Lisa Osborne
This research was supported by grants from the Natural Sciences and Engineering Research Council and Crohn’s and Colitis Canada.
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