Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3

• DOI: 10.7554/elife.78601
• Publication Date: 2023-05-24T12:00:30Z
• Authors: Rémi Porte; Rita Silva-Gomes; Charlotte Theroude; Raffaella Parente; Fatemeh Asgari; Marina Sironi; Fabio Pasqualini; Sonia Valentino; Rosanna Asselta; Camilla Recordati; Marta Noemi Monari; Andrea Doni; Antonio Inforzato; Carlos Rodriguez-...; Ignacio Obando; Elena Colino; Barbara Bottazzi; Alberto Mantovani
• Keywords: Inflammation; QH301-705.5; Neutrophils; Science; Q; R; Pentraxin 3; endothelial cells; Pneumococcal Infections; 3. Good health; Mice; Immunology and Inflammation; Streptococcus pneumoniae; neutrophils; Phagocytosis; inflammation; Animals; Mice; Inflammation/metabolism; Neutrophils/metabolism; Phagocytosis; Pneumococcal Infections/genetics; Pneumococcal Infections/metabolism; Streptococcus pneumoniae; P-selectin; Pentraxin 3; endothelial cells; immunology; infectious disease; inflammation; microbiology; mouse; neutrophils; Medicine; Animals; P-selectin; Biology (General)

Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3−/− mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.