Good Bacteria Keeps The Immune
System Primed to Fight Future Infections
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
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 Jeffrey 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 Thomas Clarke, PhD, a postdoctoral fellow
in the Weiser lab, recently published their findings in Nature
"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.
February 4, 2010