Discovery of an innate immunological memory in the intestine

Date:
February 28, 2022
Source:
Institut Pasteur
Summary:
The innate immune system plays a crucial role in regulating
host-microbe interactions, and especially in providing protection
against pathogens that invade the mucosa. Using an intestinal
infection model, scientists discovered that innate effector
cells -- group 3 innate lymphoid cells - - act not only during
the early stages of infection but can also be trained to develop
an innate form of immunological memory that can protect the host
during reinfection.



FULL STORY ==========================================================================
The innate immune system plays a crucial role in regulating host-microbe interactions, and especially in providing protection against pathogens
that invade the mucosa. Using an intestinal infection model, scientists
from the Institut Pasteur and Inserm discovered that innate effector
cells -- group 3 innate lymphoid cells -- act not only during the early
stages of infection but can also be trained to develop an innate form of immunological memory that can protect the host during reinfection. The
study was published in the journal Science on February 25, 2022.


========================================================================== Combating Escherichia coli infections, which are responsible for
intestinal diseases or gastrointestinal bleeding, is a major public
health challenge.

These bacteria, which are present in drinking water or food, can cause persistent diarrhea associated with acute intestinal inflammation.

Consequently, enteropathogenic and enterohemorrhagic Escherichia coli
are responsible for nearly 9% of child deaths worldwide.

The gut mucosa harbors a complex defense system that allows it to combat pathogen infection while maintaining tolerance to commensal microbiota,
which are essential for the normal bodily function. This constant
surveillance is performed by the innate immune system, which provides
early defense in the initial hours after infection. The adaptive immune
system then develops a memory for the pathogens that it encounters
by activating specific receptors expressed at the surface of B and T lymphocytes, thereby enabling the production of protective antibodies
and inflammatory cytokines. Unlike the clearly established function of
the adaptive system in long-term tolerance and protection, the role of
the innate system in immune memory remains to be determined.

In 2008, the team led by Inserm scientist James Di Santo (Innate Immunity
Unit, Institut Pasteur/Inserm) described group 3 innate lymphoid cells
(ILC3s) as a novel family of lymphocytes that were distinct from adaptive
T and B lymphocytes. ILC3s play an essential role in the innate immune response, especially in the gut mucosa, by producing pro-inflammatory cytokines, such as interleukin (IL)-22. The cytokine release activates
the production of antimicrobial peptides by epithelial cells, thereby
reducing the bacterial load in order to maintain the integrity of the intestinal barrier.

In this study, scientists from the Innate Immunity Unit (Institut
Pasteur/ Inserm) used an innovative protocol to expose the immune system
to a time- restricted enterobacterial challenge based on Citrobacter
rodentium (a mouse model of E. coli infection). They observed that
ILC3s persist for several months in an activated state after exposure
to C. rodentium. During a second infection, the "trained" ILC3s have a
superior capacity to control infection through an enhanced proliferation
and massive production of IL-22. "Our research demonstrates that
intestinal ILC3s acquire a memory to strengthen gut mucosal defenses
against repeated infections over time," explains Nicolas Serafini, first
author of the study and an Inserm scientist in the Innate Immunity Unit (Institut Pasteur/Inserm).

"The ability to "train" the innate immune system in the mucosa paves the
way for improvements to the body's defenses against a variety of pathogens
that cause human diseases," comments James Di Santo, last author of the
study and Head of the Innate Immunity Unit (Institut Pasteur/Inserm).

This discovery demonstrates a new antibacterial immune defense mechanism
and could lead, in the long term, to novel therapeutic approaches to
treat intestinal diseases (IBD or cancer).

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


========================================================================== Journal Reference:
1. Nicolas Serafini, Ange'lique Jarade, Laura Surace, Pedro Goncalves,
Odile
Sismeiro, Hugo Varet, Rachel Legendre, Jean-Yves Coppee, Olivier
Disson, Scott K. Durum, Gad Frankel, James P. Di Santo. Trained
ILC3 responses promote intestinal defense. Science, 2022; 375
(6583): 859 DOI: 10.1126/ science.aaz8777 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220228125617.htm

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