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Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion
- Source :
- Emerging Microbes & Infections
- Publication Year :
- 2019
- Publisher :
- Taylor & Francis, 2019.
-
Abstract
- Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor β-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection.
- Subjects :
- 0301 basic medicine
Epidemiology
animal diseases
medicine.disease_cause
Mice
Drug Discovery
Pathogen
Escherichia coli Infections
Kinase
Escherichia coli Proteins
Protein Tyrosine Phosphatase, Non-Receptor Type 6
General Medicine
MAP Kinase Kinase Kinases
Infectious Diseases
Enterohemorrhagic Escherichia coli
Host-Pathogen Interactions
SHP-1
Phosphorylation
Protein Binding
Virulence Factors
TAK1
030106 microbiology
Immunology
chemical and pharmacologic phenomena
Receptors, Cell Surface
Biology
Microbiology
Article
03 medical and health sciences
Immune system
Virology
medicine
Animals
Humans
Colitis
Escherichia coli
Immune Evasion
biochemical phenomena, metabolism, and nutrition
Evasion (ethics)
medicine.disease
ITIM
Tir
Mice, Inbred C57BL
030104 developmental biology
HEK293 Cells
RAW 264.7 Cells
Macrophages, Peritoneal
bacteria
EHEC
Parasitology
Transforming growth factor
Subjects
Details
- Language :
- English
- ISSN :
- 22221751
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Emerging Microbes & Infections
- Accession number :
- edsair.doi.dedup.....a5d7e6d4ff8e79c084710840c661712a