title: The therapeutic potential of the humoral pattern recognition molecule PTX3 in chronic lung infection caused by Pseudomonas aeruginosa.
abstract: Chronic lung infections by Pseudomonas aeruginosa strains are a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Although there is no clear evidence for a primary defect in the immune system of CF patients, the host is generally unable to clear P. aeruginosa from the airways. PTX3 is a soluble pattern recognition receptor that plays nonredundant roles in the innate immune response to fungi, bacteria, and viruses. In particular, PTX3 deficiency is associated with increased susceptibility to P. aeruginosa lung infection. To address the potential therapeutic effect of PTX3 in P. aeruginosa lung infection, we established persistent and progressive infections in mice with the RP73 clinical strain RP73 isolated from a CF patient and treated them with recombinant human PTX3. The results indicated that PTX3 has a potential therapeutic effect in P. aeruginosa chronic lung infection by reducing lung colonization, proinflammatory cytokine levels (CXCL1, CXCL2, CCL2, and IL-1β), and leukocyte recruitment in the airways. In models of acute infections and in in vitro assays, the prophagocytic effect of PTX3 was maintained in C1q-deficient mice and was lost in C3- and Fc common γ-chain-deficient mice, suggesting that facilitated recognition and phagocytosis of pathogens through the interplay between complement and FcγRs are involved in the therapeutic effect mediated by PTX3. These data suggested that PTX3 is a potential therapeutic tool in chronic P. aeruginosa lung infections, such as those seen in CF patients.
authors: Department of Immunology and Inflammation, Istituto Clinico Humanitas, Scientific Institute for Hospitalization and Cure, 20089Rozzano, Italy.
authors: Federica
authors: F
authors: Moalli
authors: Moira
authors: M
authors: Paroni
authors: Tania
authors: T
authors: Véliz Rodriguez
authors: Federica
authors: F
authors: Riva
authors: Nadia
authors: N
authors: Polentarutti
authors: Barbara
authors: B
authors: Bottazzi
authors: Sonia
authors: S
authors: Valentino
authors: Stefano
authors: S
authors: Mantero
authors: Manuela
authors: M
authors: Nebuloni
authors: Alberto
authors: A
authors: Mantovani
authors: Alessandra
authors: A
authors: Bragonzi
authors: Cecilia
authors: C
authors: Garlanda
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000627:therapeutic use*; D002908:Chronic Disease; D005455:Fluorescent Antibody Technique; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology; D000683:Serum Amyloid P-Component / Q000627:therapeutic use*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D007155:Immunologic Factors; D000683:Serum Amyloid P-Component; D000099153:Pentraxins