Streptococcus suis synthesizes deoxyadenosine and adenosine by 5'-nucleotidase to dampen host immune responses.
Virulence
; 9(1): 1509-1520, 2018.
Article
em En
| MEDLINE
| ID: mdl-30221577
ABSTRACT
Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5'-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 5'-nucleotidase not only enables producing 2'-deoxyadenosine from 2'-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2'-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 2'-deoxyadenosine by 5'-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in vivo infection experiment showed that 2'-deoxyadenosine synthesized by 5'-nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome analysis in mouse blood showed the inhibitory effect of 5'-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that S. suis synthesizes 2'-deoxyadenosine and adenosine by 5'-nucleotidase to dampen host immune responses, which represents a new mechanism of S. suis pathogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Estreptocócicas
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5'-Nucleotidase
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Adenosina
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Desoxiadenosinas
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Streptococcus suis
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Interações Hospedeiro-Patógeno
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article