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

Some “hypervirulent” strains of Listeria monocytogenes have a better capability to contaminate the central nervous system. Scientists from the Institut Pasteur, Université Paris Cité, Inserm and the Paris Public Hospital Community (AP-HP) have found a mechanism that permits cells contaminated with Listeria monocytogenes to flee immune responses. This mechanism supplies contaminated cells circulating within the blood with the next chance of adhering to and infecting cells of cerebral vessels, thereby enabling micro organism to cross the blood-brain barrier and infect the mind. The examine might be printed in Nature on March 16, 2022.

The central nervous system is separated from the bloodstream by a physiological barrier referred to as the blood-brain barrier, which may be very tight. However some pathogens handle to cross it and are due to this fact in a position to infect the central nervous system, utilizing mechanisms that aren’t but nicely understood.

Listeria monocytogenes is the bacterium answerable for human listeriosis, a extreme foodborne sickness that may result in a central nervous system an infection referred to as neurolisteriosis. This central nervous system an infection is especially critical, proving deadly in 30% of circumstances.

Scientists from the Biology of An infection Unit on the Institut Pasteur (Université Paris Cité, Inserm) and the Listeria Nationwide Reference Middle and WHO Collaborating Middle led by Marc Lecuit (Université Paris Cité and Necker-Enfants Malades Hospital (AP-HP)) just lately found the mechanism by which Listeria monocytogenes infects the central nervous system. They developed a clinically related experimental mannequin that reproduces the totally different phases of human listeriosis, and includes virulent strains of Listeria remoted from sufferers with neurolisteriosis.

The scientists first noticed that inflammatory monocytes, a kind of white blood cell, are contaminated by the micro organism. These contaminated monocytes flow into within the bloodstream and cling to the cerebral vessels’ cells, permitting Listeria to contaminate the mind tissue.

The analysis group then demonstrated that InIB, a Listeria monocytogenes floor protein, permits the micro organism to evade the immune system and survive within the protecting area of interest offered by the contaminated monocytes. The interplay between InlB and its mobile receptor c-Met blocks the cell loss of life mediated by cytotoxic T lymphocytes, which particularly goal Listeria-infected cells. InIB due to this fact permits contaminated cells to outlive cytotoxic T lymphocytes.

This mechanism extends the life span of contaminated cells, elevating the variety of contaminated monocytes within the blood and facilitating bacterial unfold to host tissues, together with the mind. It additionally favors the persistence of Listeria within the intestine tissue, its fecal excretion and transmission again to the atmosphere.

“We found a particular, surprising mechanism by which a pathogen will increase the life span of the cells it infects by particularly blocking an immune system operate that’s essential for controlling an infection,” explains Marc Lecuit (Université Paris Cité and Necker-Enfants Malades Hospital (AP-HP)), head of the Biology of An infection Unit on the Institut Pasteur (Université Paris Cité, Inserm).

It’s attainable that different intracellular pathogens akin to Toxoplasma gondii and Mycobacterium tuberculosis use related mechanisms to contaminate the mind. Figuring out and understanding the immune escape mechanisms of contaminated cells might give rise to new therapeutic methods to forestall an infection and in addition pave the best way for brand new immunosuppressive approaches for organ transplantation.

This analysis was funded by the Institut Pasteur, Inserm and the European Analysis Council (ERC) and in addition obtained funding from the Le Roch-Les Mousquetaires Basis.

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