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The role of the microbiota in preventing allergies | Institut Pasteur
http://www.pasteur.fr/en/institut-pasteur/press/press-documents/role-microbiota-preventing-allergies

The role of the microbiota in preventing allergies

The human body is inhabited by billions of symbiotic bacteria, carrying a
diversity that is unique to each individual. The microbiota is involved in
many mechanisms, including digestion, vitamin synthesis and host defense.
It is well established that a loss of bacterial symbionts promotes the
development of allergies. Scientists at the Institut Pasteur have succeeded
in explaining this phenomenon, and demonstrate how the microbiota acts on
the balance of the immune system: the presence of microbes specifically
blocks the immune cells responsible for triggering allergies. These results
are published in Science.

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http://www.pasteur.fr/en/institut-pasteur/press/press-documents/role-microbiota-preventing-allergies

Press release
Paris, July 10, 2015
Dans le colon de souris, un amas de cellules de type 3 (en vert). ©
Institut Pasteur

The hygiene hypothesis[1] suggests a link between the decline in infectious
diseases and the increase in allergic diseases in industrialized countries.
Improvements in hygiene levels necessarily lead to reduced contact with
microbes that is paralleled by an increased incidence in allergic and
autoimmune diseases, such as type 1 diabetes.

Epidemiological studies have substantiated this hypothesis, by showing that
children living in contact with farm animals – and therefore with more
microbial agents – develop fewer allergies during their lifetime.
Conversely, experimental studies have shown that administering antibiotics
to mice within the first days of life results in a loss of microbiota, and
subsequently, in an increased incidence in allergy.

However, until now, the biological mechanisms underlying this phenomenon
remained unclear. In this study published in Science, the team led by
Gérard Eberl (head of the Microenvironment and Immunity Unit at the
Institut Pasteur) shows that, in mice, symbiotic intestinal microbes act on
the immune system by blocking allergic reactions.

Several types of immune response can be generated in order to defend the
organism. The presence of bacterial or fungal microbes provokes a response
from immune cells known as type 3 cells. These immune cells coordinate the
phagocytosis and killing of the microbes. However, in the case of infection
by pathogenic agents that are too large to be handled by type 3 cells (such
as parasitic worms and certain allergens), the cells that organize the
elimination of the pathogen, but also allergic reactions, are known as type
2 cells.

In this study, scientists at the Institut Pasteur have shown that type 3
cells activated during a microbial aggression act directly on type 2 cells
and block their activity. Type 2 cells are consequently unable to generate
allergic immune responses. This work demonstrates that the microbiota
indirectly regulates type 2 immune responses by inducing type 3 cells.

These results explain how an imbalance in microbiota triggers an
exaggerated type 2 immune response normally used to fight large parasites,
but that also leads to allergic responses.

These findings represent an important milestone in understanding the
balance between our various defense mechanisms. In terms of allergy
treatment, a hitherto unexplored therapeutic approach consists therefore in
stimulating type 3 cells by mimicking a microbial antigen in order to block
allergy-causing type 2 cells.

These studies were funded by the French National Agency for Research, the
French Medical Research Foundation, the Simone & Cino Del Duca Foundation,
the European Commission and the “Integrative Biology of Emerging Infectious
Diseases” Laboratory of Excellence.

Illustration: A cluster of type 3 cells (shown in green) in a mouse colon.
These cells are induced by the microbiota and block type 2 allergic
reactions. © Institut Pasteur

Source

The microbiota regulates type 2 immunity through RORgt+ T cells, Science,
July 9, 2015

Caspar Ohnmacht1*, Joo-Hong Park1*, Sascha Cording1, James B. Wing2, Koji
Atarashi3,4, Yuuki Obata5, Valérie Gaboriau-Routhiau6,7,8, Rute Marques1,
Sophie Dulauroy1, Maria Fedoseeva9, Meinrad Busslinger10, Nadine
Cerf-Bensussan6,7, Ivo G. Boneca11,12, David Voehringer13, Koji Hase5,
Kenya Honda3,14, Shimon Sakaguchi2,15, Gérard Eberl1‡

1 Institut Pasteur, Microenvironment & Immunity Unit, 75724 Paris, France
2 Laboratory of Experimental Immunology, Immunology Frontier Research
Center, Osaka University, Suita 565-0871, Japan
3 RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama,
Kanagawa 230-0045, Japan
4 PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan
5 The Institute of Medical Science, The University of Tokyo, Tokyo
108-8639, Japan
6 INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France
7 Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine,
Paris, France
8 INRA Micalis UMR1319, Jouy-en-Josas, France
9 Center of Allergy and Environment (ZAUM), Technische Universität and
Helmholtz Zentrum München, Munich, Germany
10 Research Institute of Molecular Pathology, Vienna Biocenter, 1030
Vienna, Austria
11 Institut Pasteur, Biology and Genetics of Bacterial Cell Wall, 75724
Paris, France
12 INSERM, Groupe Avenir, 75015 Paris, France
13 Department of Infection Biology at the Institute of Clinical
Microbiology, Immunology and Hygiene, University Clinic Erlangen and
Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany
14 CREST, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi,
Saitama 332-0012, Japan
15 Department of Experimental Pathology, Institute for Frontier Medical
Sciences, Kyoto University, Kyoto 606-8507, Japan.

   - Ces auteurs ont contribué équitablement à ce travail. ‡ Main author

[1] J. F. Bach, The effect of infections on susceptibility to autoimmune
and allergic diseases. N Engl J Med 347, 911 (2002).

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