Israeli study sparks new research into fighting infectious diseases in babies
The need to let helpful microbes do their work weakens a baby’s immune system, a problem challenging an Israeli scientist.
That babies are especially sensitive to bacterial infections isn’t news. According to the World Health Organization, more than 2 million babies under six months old die of such infections every year.
The womb is a sterile environment, but the moment the baby moves into the birth canal, bacteria, viruses and fungi tax the little one’s immune system. The body developed this sensitivity to let helpful microorganisms colonize the intestines, skin, mouth and lungs.
A study published in the journal Nature last month discusses possible ways to help a newborn’s immune system fight infections better, while making vaccinations more effective. The study was based in part on research by Israeli professor Ofer Levy, a pediatric specialist in infectious diseases from Boston Children’s Hospital and Harvard Medical School, though he isn’t one of the authors.
The researchers examined why newborns have such a weak immune system. One answer is that during the first weeks of life, babies have large quantities of a kind of red blood cell known as CD71+. These cells block the white blood cells that fight off foreign invaders in the body. So the baby’s response to infections, and perhaps also to certain vaccinations, is weakened.
But this disadvantage has an upside: If the immune system reacted too strongly, the baby’s body might be harmed.
“At very young ages, the immune system is weak because the white blood cells respond weakly to bacteria,” Levy told Haaretz. “The basic reason for this is a process during pregnancy, when there’s a biological need to prevent an immunological war between the mother and the fetus. The baby is initially sterile, but in the first moments after birth many bacteria begin accumulating in his body – on his skin and in his mouth, stomach and intestines. In this situation, it’s very important that his immune system not respond with inflammation.”
In other words, the baby’s immune system must start off weak because of the need to prevent inflammation – the body’s response to dangers such as bacteria or trauma. If, for instance, a baby’s immune system reacted too strongly to a skin rash during his first days of life, his skin could rupture. On the other hand, a weak immune system increases the risk of infection.
A baby’s weakened immune system also weakens the response to certain vaccinations. After being vaccinated, the body normally develops antibodies against harmful invaders. But the immune system’s weak response shortly after birth means that only a moderate quantity of antibodies will develop – and this makes some vaccines less effective, Levy explained.
For this reason, babies are usually not vaccinated until several months after birth. But the study’s authors noted that if a way could be found to strengthen babies’ immune systems – for instance, by reducing the number of CD71+ cells or by introducing molecules that strengthen the immune system’s response – babies could be vaccinated immediately after birth. That would be helpful in developing countries, where birth may be the only time a baby receives medical attention.
In the Nature study, when immune cells of 6-day-old mice were compared with those of adult mice, the babies had a higher proportion of CD71+ cells. These cells suppressed the immune system by creating an enzyme called arginase.
Next, the researchers injected the baby mice with antibodies that caused their immune systems to destroy the CD71+ cells. They then injected the mice with the Listeria monocytogenes bacterium, which causes serious infections, especially in newborns.
The mice’s immune system repelled the bacterial attack easily, but with severe side effects: Lacking the CD71+ cells, their intestinal cells became inflamed upon contact with the bacteria. The researchers also discovered that human umbilical-cord blood contains more CD71+ cells than the blood of adult humans.
Now the researchers are trying to find ways to intervene in newborns’ immune systems to make it easier to treat infectious diseases. For instance, premature babies sometimes suffer from necrotizing enterocolitis, a condition that causes their intestines to fall apart, thought to be caused by a lack of the bacteria that enable people to digest food.
The researchers say these preemies may not yet have developed the DC71+ cells that would moderate their immune response and enable the helpful digestive bacteria to colonize their intestines. If so, finding a way to cause these cells to develop, or to activate them if they are merely dormant, could temporarily suppress the immune response until the requisite bacterial colonization has occurred.
But Levy says further research is needed before the study’s results can be put into practice. The body’s microbial ecosystem is intertwined with its immune system, so it’s hard to make changes in one without disrupting the other.
For now, Levy advises sticking to the existing vaccination protocols but hopes that these inoculations can be made even more effective. His lab is planning a study, with more than $3 million in funding from Bill Gates, to try to create vaccines that will be both safe and effective immediately after birth.
“We’re sampling the immune cells of both adults and babies to examine their differing immune response; in this way we can study the possible responses to [vaccines] that haven’t yet gone into use – for instance, vaccinations against HIV or tuberculosis,” he said. “In addition, we’re trying to turn some vaccines that already exist into a single, concentrated vaccine that could be effective in the first days after birth.”
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