Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection

Shigella spp.are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation.Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity.Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3.In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum.PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella.In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity.These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis.Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity. Author summarySoluble pattern recognition molecules, PRMs, are components of the humoral arm of innate immunity.The long pentraxin 3, PTX3, is a prototypic soluble PRM that is produced in response to primary inflammatory signals.Shigella spp.are human enteropathogens which invade colonic and rectal mucosa where they cause deleterious inflammation.We show that PTX3 acts as an ante-antibody and contributes to the clearance of extracellular Shigella.As a countermeasure, Shigella uses invasiveness and low-inflammatory LPS to control PTX3 release in infected cells.