'Good' Bacteria Keep Immune System Primed to Fight Future Infections

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http://www.sciencedaily.com/releases/2010/01/100127095945.htm

So where does one get this " Nod1 ligand " ?

-Sunil

'Good' Bacteria Keep Immune System Primed to Fight Future Infections

ScienceDaily (Feb. 3, 2010) — Scientists have long pondered the

seeming contradiction that taking broad-spectrum antibiotics over a

long period of time can lead to severe secondary bacterial infections.

Now researchers from the University of Pennsylvania School of Medicine

may have figured out why.

The investigators show that " good " bacteria in the gut keep the immune

system primed to more effectively fight infection from invading

pathogenic bacteria. Altering the intricate dynamic between resident

and foreign bacteria -- via antibiotics, for example -- compromises an

animal's immune response, specifically, the function of white blood

cells called neutrophils.

Senior author Weiser, MD, professor of Microbiology and

Pediatrics, likens these findings to starting a car: It's much easier

to start moving if a car is idling than if its engine is cold.

Similarly, if the immune system is already warmed up, it can better

cope with pathogenic invaders. The implication of these initial

findings in animals, he says, is that prolonged antibiotic use in

humans may effectively throttle down the immune system, such that it

is no longer at peak efficiency.

" Neutrophils are being primed by innate bacterial signals, so they are

ready to go if a microbe invades the body, " Weiser explains. " They are

sort of 'idling', and the baseline system is already turned on. "

Weiser and first author e, PhD, a postdoctoral fellow in

the Weiser lab, recently published their findings in Nature Medicine.

" One of the complications of antibiotic therapy is secondary

infection, " Weiser explains. " This is a huge problem in hospitals, but

there hasn't been a mechanistic understanding of how that occurs. We

suggest that if the immune system is on idle, and you treat someone

with broad-spectrum antibiotics, then you turn the system off. The

system is deprimed and will be less efficient at responding quickly to

new infections. "

The findings also provide a potential explanation for the anecdotal

benefits of probiotic therapies because keeping your immune system

primed by eating foods enhanced with " good " bacteria may help

counteract the negative effects of sickness and antibiotics.

Researchers have for many years understood that most bacteria in the

body are not " bad. " In fact, humans (and mice) have a symbiotic

relationship with their resident microbes that significantly impacts,

among other things, metabolism and weight homeostasis. As shown in

this study, microbes also affect the innate immune response, via the

cellular protein Nod1.

Present within neutrophils, Nod1 is a receptor that recognizes parts

of the cell wall of bacteria. Weiser and his colleagues found that

neutrophils derived from mice engineered to lack Nod1 are less

effective at killing two common pathogens, Streptococcus pneumoniae

and Staphylococcus aureus, than neutrophils from mice that do express

the receptor.

In addition, neutrophils from mice that were raised in a germ-free

environment or on antibiotics were likewise diminished in their immune

responses, but this effect was not permanent: Re-exposure of these

mice to a conventional environment (that is, one containing normal

bacteria) restored immune function.

The team provided evidence for a potential mechanism for these

observations by showing that bacterial cell wall material could be

detected in the blood of normal mice, and that it influences

neutrophils in the bone marrow. Finally, the team demonstrated they

could improve immune function by treating both antibiotic-treated mice

and human neutrophils with the Nod1 ligand -- a finding that suggests

it may be possible to counter the adverse consequences of antibiotics

in humans.

The study was funded by the US Public Health Service.

Story Source:

Adapted from materials provided by University of Pennsylvania School

of Medicine.