Allergy study on ‘wild’ mice challenges the hygiene hypothesis

picture:

How microbes can prevent allergies has attracted a lot of attention recently. Studies suggest that some infections can reduce the production of inflammatory antibodies against allergens and change the behavior of T cells involved in allergies. It has also been suggested that the good bacteria in our gut can prevent inflammation in other parts of the body.

Strong allergic reactions

Researchers have now compared the allergic immune response in “dirty” wild mice with that of typical clean laboratory mice. They found little evidence that the antibody response changed or that T-cell function changed in any meaningful way. Also, the anti-inflammatory responses triggered by good gut bacteria do not seem to be able to stop the allergic immune response. In contrast, wild-type mice showed strong signs of pathological inflammation and allergic reactions when exposed to allergens.

This was somewhat unexpected, but it suggests that it’s not as simple as saying, “A dirty lifestyle will stop allergies while a clean lifestyle can trigger them.” There may be very specific contexts where this is true, but it’s probably not a general rule, says Jonathan Coquet, co-author of the study and associate professor in the Department of Microbiology, Oncology and Cell Biology at Karolinska Institutet.

More like the human immune system

The wild mice in the study are genetically identical to pure laboratory mice but live in near-natural conditions and are exposed to a rich microbiome from birth.

“The immune systems of these wild mice better represent the human immune system, so we hope they will bring us closer to the truth about how microbes affect the body,” says Jonathan Coquet.

The findings contribute to our general understanding of how allergies arise and may also have clinical implications. In clinical trials, researchers and doctors have recently tried to treat patients with inflammatory diseases with experimental infections. For example, deworming or fecal transplants have been proposed as tools to combat inflammatory diseases. Newborns born by cesarean section underwent fecal transplantation and received bacterial supplements in order to promote good bacteria in the baby’s gut and the baby’s future health.

It can provide important insights

This area of ​​research can provide important insights into how infections and microbes can be used to improve health, but it is still in its infancy. “Our study is a reminder that broad, general exposure to microbes may not have the clear positive effects we hope it will,” says Susan Nylen, study co-author and associate professor in the Department of Microbiology, Oncology and Cell Biology. At Karolinska Institutet.

ejaculate:
This work was led by Junjie Ma and Egon Ørgaard, researchers in Jonathan Coquet’s group, and was carried out in close collaboration with Professor Stefan Rosshart at the University Medical Center Freiburg in Germany and Susanne Nylen (MTC). Several other research groups at Karolinska Institutet and elsewhere also contributed to this work, including the teams of Assistant Professors Itziar Martínez González and Juan Do (both in the Department of Microbiology, Oncology and Cell Biology, MTC).

The study was funded by several bodies, including the Swedish Research Council, the Cancer Foundation, internal funds of KI and the Wenner Gren Foundation.

Publishing

“Laboratory mice with wild-type microorganisms generate robust allergic immune responses.”, Junjie Ma, Egon Ørgaard, Solveig Runge, Kajsa H. Clason, Laura Matha, Julian M. Stark, Leiqin Cheng, Javiera Alvarez, Silvia von Zedtwitz, Ostia Pallivisut, Sergio Martinez Høyer, Mozin Li, Anne-Marlene Gernand, Lisa Ospelt, Agata Anna Bjelica, Till R. Lisker, Huey J. Huang, Susanne Fertala, Louis Bohn, Rudi Baert, Mikael Adner, Itziar Martinez Gonzalez, Till Stroege, Juan Du, Susan Nylin, Stefan B. Rosehart, Jonathan M. Coquet, Immunologyonline 29 September 2023, doi: 10.1126/sciimmunol.adf7702.