Streptococcus suis synthesizes deoxyadenosine and adenosine by 5'-nucleotidase to dampen host immune responses

Area of Science:

• Microbiology
• Immunology
• Pathogenesis

Background:

• Streptococcus suis is a significant bacterial pathogen in pigs and an emerging zoonotic agent.
• S. suis 5 -nucleotidase is a known virulence factor that inhibits neutrophil functions by converting adenosine monophosphate to adenosine.
• The precise mechanisms by which S. suis evades host immunity require further elucidation.

Purpose of the Study:

• To investigate the enzymatic activity of S. suis 5 -nucleotidase in producing deoxyadenosine and adenosine.
• To determine the in vivo effects of these nucleosides on host immune cells and responses.
• To elucidate the role of S. suis 5 -nucleotidase in bacterial pathogenesis.

Main Methods:

• Enzymatic assays and reversed-phase high-performance liquid chromatography (RP-HPLC) for in vitro analysis.
• RP-HPLC and liquid chromatography with tandem mass spectrometry for in vivo nucleoside detection in mouse blood.
• Cellular cytotoxicity assays, Western blot analysis, in vivo infection experiments, and in vivo transcriptome analysis in mice.

Main Results:

• S. suis 5 -nucleotidase produced 2 -deoxyadenosine from 2 -deoxyadenosine monophosphate in vitro and in vivo.
• 2 -deoxyadenosine induced caspase-3-dependent death of mouse macrophages (RAW 264.7).
• In vivo, S. suis infection led to monocytopenia and suppressed neutrophil functions, likely mediated by adenosine.

Conclusions:

• S. suis 5 -nucleotidase synthesizes both 2 -deoxyadenosine and adenosine, representing a novel mechanism for dampening host immune responses.
• The enzyme contributes to S. suis pathogenesis by triggering immune cell death and dysfunction.
• These findings highlight a new strategy employed by S. suis to evade the host immune system.