Discovery of an immune escape mechanism promoting Listeria infection of
the central nervous system

Date:
March 16, 2022
Source:
Institut Pasteur
Summary:
Some 'hypervirulent' strains of Listeria monocytogenes have a
greater capacity to infect the central nervous system. Scientists
have discovered a mechanism that enables cells infected with
Listeria monocytogenes to escape immune responses. This mechanism
provides infected cells circulating in the blood with a higher
probability of adhering to and infecting cells of cerebral vessels,
thereby enabling bacteria to cross the blood-brain barrier and
infect the brain.



FULL STORY ==========================================================================
Some "hypervirulent" strains of Listeria monocytogenes have a greater
capacity to infect the central nervous system. Scientists from the
Institut Pasteur, Universite' Paris Cite', Inserm and the Paris Public
Hospital Network (AP-HP) have discovered a mechanism that enables cells infected with Listeria monocytogenes to escape immune responses. This
mechanism provides infected cells circulating in the blood with a higher probability of adhering to and infecting cells of cerebral vessels,
thereby enabling bacteria to cross the blood-brain barrier and infect
the brain. The study will be published in Nature on March 16, 2022.


==========================================================================
The central nervous system is separated from the bloodstream by a
physiological barrier known as the blood-brain barrier, which is very
tight. But some pathogens manage to cross it and are therefore able to
infect the central nervous system, using mechanisms that are not yet
well understood.

Listeria monocytogenes is the bacterium responsible for human listeriosis,
a severe foodborne illness that can lead to a central nervous system
infection known as neurolisteriosis. This central nervous system infection
is particularly serious, proving fatal in 30% of cases.

Scientists from the Biology of Infection Unit at the Institut Pasteur (Universite' Paris Cite', Inserm) and the Listeria National Reference
Center and WHO Collaborating Center led by Marc Lecuit (Universite' Paris
Cite' and Necker-Enfants Malades Hospital (AP-HP)) recently discovered
the mechanism by which Listeria monocytogenes infects the central nervous system. They developed a clinically relevant experimental model that
reproduces the different stages of human listeriosis, and involves
virulent strains of Listeria isolated from patients with neurolisteriosis.

The scientists first observed that inflammatory monocytes, a type of
white blood cell, are infected by the bacteria. These infected monocytes circulate in the bloodstream and adhere to the cerebral vessels' cells, allowing Listeria to infect the brain tissue.

The research team then demonstrated that InIB, a Listeria
monocytogenessurface protein, enables the bacteria to evade the immune
system and survive in the protective niche provided by the infected
monocytes. The interaction between InlB and its cellular receptor
c-Met blocks the cell death mediated by cytotoxic T lymphocytes, which specifically targetListeria-infected cells. InIB therefore enables
infected cells to survive cytotoxic T lymphocytes.

This mechanism extends the life span of infected cells, raising the number
of infected monocytes in the blood and facilitating bacterial spread to
host tissues, including the brain. It also favors the persistence of
Listeria in the gut tissue, its fecal excretion and transmission back
to the environment.

"We discovered a specific, unexpected mechanism by which a pathogen
increases the life span of the cells it infects by specifically blocking
an immune system function that is crucial for controlling infection,"
explains Marc Lecuit (Universite' Paris Cite' and Necker-Enfants Malades Hospital (AP-HP)), head of the Biology of Infection Unit at the Institut Pasteur (Universite' Paris Cite', Inserm).

It is possible that other intracellular pathogens such as Toxoplasma
gondii and Mycobacterium tuberculosis use similar mechanisms to infect
the brain.

Identifying and understanding the immune escape mechanisms of infected
cells could give rise to new therapeutic strategies to prevent infection
and also pave the way for new immunosuppressive approaches for organ transplantation.

This research was funded by the Institut Pasteur, Inserm and the European Research Council (ERC) and also received funding from the Le Roch-Les Mousquetaires Foundation.


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


========================================================================== Journal Reference:
1. Claire Maudet, Marouane Kheloufi, Sylvain Levallois, Julien
Gaillard, Lei
Huang, Charlotte Gaultier, Yu-Huan Tsai, Olivier Disson, Marc
Lecuit.

Bacterial inhibition of Fas-mediated killing promotes neuroinvasion
and persistence. Nature, 2022; DOI: 10.1038/s41586-022-04505-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220316120827.htm

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