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Streptococcus suis synthesizes deoxyadenosine and adenosine by 5’-nucleotidase to dampen host immune responses
- Source :
- Virulence, Virulence, Vol 9, Iss 1, Pp 1509-1520 (2018)
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5ʹ-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5ʹ-nucleotidase not only enables producing 2ʹ-deoxyadenosine from 2ʹ-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2ʹ-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2ʹ-deoxyadenosine by 5ʹ-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in vivo infection experiment showed that 2ʹ-deoxyadenosine synthesized by 5ʹ-nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome analysis in mouse blood showed the inhibitory effect of 5ʹ-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that S. suis synthesizes 2ʹ-deoxyadenosine and adenosine by 5ʹ-nucleotidase to dampen host immune responses, which represents a new mechanism of S. suis pathogenesis.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Adenosine monophosphate
Adenosine
Streptococcus suis
Neutrophils
Virulence Factors
2ʹ-deoxyadenosine
030106 microbiology
Immunology
Biology
5ʹ-nucleotidase
Microbiology
immune response
lcsh:Infectious and parasitic diseases
5'-nucleotidase
Mice
03 medical and health sciences
chemistry.chemical_compound
Immune system
Bacterial Proteins
monocytopenia
Deoxyadenosine
In vivo
Streptococcal Infections
Nucleotidase
medicine
Animals
lcsh:RC109-216
5'-Nucleotidase
Deoxyadenosines
Gene Expression Profiling
Macrophages
biology.organism_classification
RAW 264.7 Cells
Infectious Diseases
chemistry
Host-Pathogen Interactions
Female
Parasitology
Research Paper
medicine.drug
Subjects
Details
- ISSN :
- 21505608 and 21505594
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Virulence
- Accession number :
- edsair.doi.dedup.....43e102c35c6e5d0ca2f5f4bb2d63b8d1