Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes

Autor: Philip P. Ostrowski, John H. Brumell, Taoyingnan Li, Catherine J. Greene, Dustin A. Ammendolia, Brian Raught, Adam R R McCluggage, Monica E Garner, Darren E. Higgins, James M. Regeimbal, Marija Cemma, Joel M J Tan, Katherine J. Wu, Sergio Grinstein, Robin M. Yates, Jorge David Rojas Márquez, Michael S. Diamond
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
General Physics and Astronomy
medicine.disease_cause
Mice
0302 clinical medicine
Interferon
Phagosomes
Listeriosis
Phagosome
Innate immunity
Mice
Knockout
0303 health sciences
Phagocytes
Multidisciplinary
Immune evasion
3. Good health
Anti-Bacterial Agents
Host-Pathogen Interactions
Interferon Type I
medicine.drug
Listeria
Virulence Factors
Science
Antiviral protein
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Microbiology
03 medical and health sciences
Immune system
Listeria monocytogenes
Viral entry
Phagosome maturation
medicine
Animals
030304 developmental biology
Intracellular parasite
Membrane Proteins
General Chemistry
Virus Internalization
Mice
Inbred C57BL
Disease Models
Animal
RAW 264.7 Cells
bacteria
Interferons
Bacterial infection
Transcriptome
030215 immunology
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)
ISSN: 2041-1723
Popis: The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.
Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.
Databáze: OpenAIRE
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