TY - JOUR
T1 - Role of a fluid-phase PRR in fighting an intracellular pathogen
T2 - PTX3 in Shigella infection
AU - Ciancarella, Valeria
AU - Lembo-Fazio, Luigi
AU - Paciello, Ida
AU - Bruno, Anna-Karin
AU - Jaillon, Sébastien
AU - Berardi, Sara
AU - Barbagallo, Marialuisa
AU - Meron-Sudai, Shiri
AU - Cohen, Dani
AU - Molinaro, Antonio
AU - Rossi, Giacomo
AU - Garlanda, Cecilia
AU - Bernardini, Maria Lina
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - Animals
KW - C-Reactive Protein/immunology
KW - Dysentery, Bacillary/immunology
KW - Humans
KW - Immunity, Innate/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - Serum Amyloid P-Component/immunology
KW - Shigella flexneri/immunology
U2 - 10.1371/journal.ppat.1007469
DO - 10.1371/journal.ppat.1007469
M3 - Article
C2 - 30532257
VL - 14
SP - e1007469
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 12
ER -