Gut bacteria essential for immune cell development

Date: Mar-13-2014A new study finds that gut bacteria play an important role in the development of

white blood cells that help the body's immune system fight infection.

The human body is home to thousands of species of microbes - collectively known as the

microbiome - that we are increasingly coming to realize are essential to health. The highest

concentration and diversity of these species is found in the gastrointestinal tract, and the

colon in particular.

With his team at the California Institute

of Technology (Caltech) in Pasadena, Sarkis Mazmanian, a professor of biology and biological engineering, has been researching this area for some

time.

Their work with mice has already led to numerous revelations about the importance of gut

bacteria to health.

For example, in 2013, they reported a groundbreaking study that linked gut

microbes to symptoms  of autism, 3 years after they revealed how gut bacteria affect multiple

sclerosis, and also how restoring their equilibrium may alleviate

inflammatory bowel disease.

Gut bacteria instrumental to development of innate immune cells

In this latest study, published in the journal Cell Host & Microbe, they

describe how they discovered that beneficial gut bacteria played a key role in the development

of innate immune cells - specifically macrophages, monocytes and neutrophils - special white

blood cells that provide a first line of defense against invading pathogens.

These white blood cells do not only circulate in the blood, they are also stored in the spleen

and in bone marrow. When the team compared counts of white blood cells in these areas in mice

born without gut bacteria - known as "germ-free" mice - and healthy mice with a normal gut

bacteria population, they found the germ-free mice had fewer of them.

The germ-free mice also had fewer stemlike cells that can differentiate into some types of

immune cells. Plus, their spleens contained defective innate immune cells whose populations

never reached the size found in healthy mice with microbes in their gut.

Gut microbes influence immunity beyond the gut

First author Arya Khosravi, a graduate student in Prof. Mazmanian's lab, says:

"It's interesting to see that these microbes are having an immune effect beyond where they

live in the gut. They're affecting places like your blood, spleen, and bone marrow - places

where there shouldn't be any bacteria."

The team tested the mice's ability to fight off infection by exposing them to the bacterium

Listeria monocytogenes, which is harmful to humans and often used in mouse studies of

the immune system.

They found the healthy mice recovered quickly after being injected with the bacterium, but

the germ-free mice died - they were not able to fight off the infection.

But when germ-free mice were then given gut bacteria typical of healthy mice, their white

cell count increased, and they survived the infection.

And in another part of the study, the team gave healthy mice antibiotics to kill their gut

bacteria and then injected them with Listeria. They got sick and had trouble fighting off the

infection.

Could antibiotics kill off gut bacteria that protect us from other infections?

The researchers say these results prompt questions about infections in humans, as Prof.

Mazmanian explains:

"For example, when patients are put on antibiotics for something like hip surgery, are you

damaging their gut microbe population and making them more susceptible to an infection that had

nothing to do with their hip surgery?"

And looking at it from the other side, could ensuring patients have healthy gut populations

offer a preventive alternative to giving them antibiotics?

This opens a new avenue for dealing with superbugs that are resistant to antibiotics.

Limiting susceptibility to infection might be a more fruitful strategy, the team suggests.

Written by Catharine Paddock PhD




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