A BYU-Harvard-Stanford research team has identified a molecule that is key to mothers’ ability to pass along immunity to intestinal infections to their babies through breast milk.
The study highlights an amazing change that takes place in a mother’s body when she begins producing breast milk. For years before her pregnancy, cells that produce antibodies against intestinal infections travel around her circulatory system as if it were a highway and regularly take an “off-ramp” to her intestine. There they stand ready to defend against infections such as cholera or rotavirus. But once she begins lactating, some of these same antibody-producing cells suddenly begin taking a different “off-ramp,” so to speak, that leads to the mammary glands. That way, when her baby nurses, the antibodies go straight to his intestine and offer protection while he builds up his own immunity.
This is why previous studies have shown that formula-fed infants have twice the incidence of diarrheal illness as breast-fed infants.
Until now, scientists did not know how the mother’s body signaled the antibody-producing cells to take the different off-ramp. The new study identifies the molecule that gives them the green light.
“Everybody hears that breastfeeding is good for the baby,” said Eric Wilson, the Brigham Young University microbiologist who is the lead author on the study. “But why is it good? One of the reasons is that mothers’ milk carries protective antibodies which shield the newborn from infection, and this study demonstrates the molecular mechanisms used by the mother’s body to get these antibody-producing cells where they need to be.”
Understanding the role of the molecule, called CCR10, also has implications for potential future efforts to help mothers better protect their infants.
“This tells us that this molecule is extremely important, so if we want to design a vaccine for the mother so she could effectively pass protective antibodies to the child, it would be absolutely essential to induce high levels of CCR10,” said Wilson.
Speaking broadly about the long-term applications of this research, BYU undergraduate Elizabeth Nielsen Low, a co-author on the paper, said, “If we know how these cells migrate, we’ll be able to hit the right targets to get them to go where we want them.”
Daniel Campbell is a researcher at the Benroya Research Institute in Seattle, a nonprofit organization that specializes in the immune system, and was not affiliated with this study.
“The molecular basis for this redistribution [of the mother’s cells] has not been well characterized, but Dr. Wilson’s work has begun to crack that code and define the molecules responsible for this cellular redistribution and passive immunity,” Campbell said. “It is important work that fundamentally enhances our understanding of how immunity is provided to the [baby] via the milk. Dr. Wilson’s study will certainly form the basis for many other studies aimed at uncovering how the immune system is organized, particularly at mucosal surfaces.”
To conduct their research, the team used so-called “knock-out mice” that had been genetically engineered to lack the CCR10 molecule. Whereas normal lactating mice had hundreds of thousands of antibody-producing cells in their mammary glands, the BYU team found that the knock-out mice had more than 70 times fewer such cells. Tests verified that the absence of CCR10 was responsible for the deficiency.
Surprisingly, the research also showed that CCR10 does not play the same crucial role in signaling antibody-producing cells to migrate to the intestine. Another molecule is their “traffic light.”
The findings will be published in the Nov. 1 issue of the Journal of Immunology.
The study was supported by Wilson’s grant from the National Institutes of Health, funding which continues for another 18 months and supports his and his students’ further investigation into the cells behind transfer of immunity in breast milk.
Wilson’s other students who are also co-authors on the paper are Yuetching Law, Kathryn Distelhorst and Erica D. Hill. The Harvard Medical School co-authors are Olivier Morteau, Craig Gerard, Bao Lu, Sorina Ghiran and Miriam Rits. The Stanford University School of Medicine co-authors are Raymond Kwan, Nicole H. Lazarus and Eugene C. Butcher.
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