Immune system keeps the intestinal flora in balance

Date:
October 13, 2021
Source:
University of Bern
Summary:
Trillions of benign bacteria live in the intestine. They are
kept in a continuous balance by the immune system, which thereby
makes them harmless to humans. Researchers have been able to show
how certain natural antibodies keep these bacteria in check. The
findings could make an important contribution to the development
of superior vaccines.



FULL STORY ==========================================================================
The bacteria living in the intestine consist of some 500 to 1000 different species. They make up what is known as the intestinal flora, which plays
a key role in digestion and prevents infections. Unlike pathogens that
invade from the outside, they are harmless and tolerated by the immune
system. The way in which the human immune system manages to maintain
this delicate balance in the intestine largely remains unknown. It
is known that type A immunoglobulins, referred to as IgA antibodies,
play an important role. These natural defense substances are part of
the immune system, and recognize an exogenous pathogen very specifically according to the lock-and-key principle.


==========================================================================
A group of researchers led by Dr. Tim Rollenske and Prof. Andrew
Macpherson from the Department of BioMedical Research (DBMR) at the
University of Bern and the University Hospital for Visceral Surgery
and Medicine at the Inselspital have recently been able to show in a
mouse model that IgA antibodies specifically limit the fitness of benign bacteria at several levels. This enables the immune system to fine-tune
the microbial balance in the intestine.

"We have succeeded in demonstrating that the immune system recognizes
and restricts these bacteria very specifically," explains Tim Rollenske,
PhD, lead author of the study. The results have been published in the
journal Nature.

IgA antibodies created in natural form for the first time IgA antibodies
are the most common antibodies in the human immune system, and are
secreted by specialist cells in the mucous membranes. They account for
two- thirds of human immunoglobulins. Surprisingly, most IgA antibodies produced by the body are directed against benign bacteria in the
intestinal flora. Without this immune protection, these microorganisms
could also have a detrimental effect on health and cause intestinal
diseases. However, the mystery of the way in which IgA antibodies regulate
the consensual coexistence in the intestine has remained unsolved.

The reason for this: Until now, studying IgA antibodies in their
natural form in animal models was not possible. In their experiment,
the researchers led by Tim Rollenske and Andrew Macpherson were able to overcome this hurdle, however.

They succeeded in producing a sufficient amount of IgA antibodies
specifically directed against a type of Escherichia coli bacteria,
a typical intestinal bacterium. The antibodies recognized and bound a
building block on the membrane of the microorganisms.

Antibodies impair the fitness of the bacteria In their experiment, which
the researchers worked on for three years, they succeeded in tracking
the in-vitro and in-vivo effect in the intestines of germ-free mice with pinpoint accuracy. The antibodies were found to affect the fitness of
the bacteria in several ways. The mobility of bacteria was restricted,
for example, or they hindered the uptake of sugar building blocks for the metabolism of the bacteria. The effect depended on the surface component
that was specifically recognized. "This means that the immune system
is apparently able to influence the benign intestinal bacteria through different approaches on a simultaneous basis," explains Hedda Wardemann
of the German Cancer Research Center, co-author. The researchers therefore speak of IgA parallelism.

The question of why the immune system achieves an equilibrium with the
benign bacteria in the intestine while effectively destroying pathogenic invaders remains to have been conclusively clarified. "However, our
experiment shows that IgA antibodies can fine-tune the balance between
the human organism and the intestinal flora," explains Andrew Macpherson
of the DBMR and Inselspital, co-author. The findings not only build on
the basic understanding of the immune system in the intestine, they can
also contribute to the development of vaccines. "Understanding exactly
how and where antibodies recognize microorganisms in the intestine will
also allow us to develop vaccines against pathogenic organisms on a more targeted basis," Tim Rollenske adds.

========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Parallelism of intestinal secretory IgA shapes functional microbial
fitness. Tim Rollenske, Sophie Burkhalter, Lukas Muerner, Stephan
von Gunten, Jolanta Lukasiewicz, Hedda Wardemann and Andrew
J. Macpherson.

Nature, 13 October 2021 DOI: 10.1038/s41586-021-03973-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211013114115.htm

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