Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant

Barbara Bottazzi; Laura Santini; Silvana Savino; Marzia M Giuliani; Ana I Dueñas Díez; Giuseppe Mancuso; Concetta Beninati; Marina Sironi; Sonia Valentino; Livija Deban; Cecilia Garlanda; Giuseppe Teti; Mariagrazia Pizza; Rino Rappuoli; Alberto Mantovani

doi:10.1371/journal.pone.0120807

Recognition of Neisseria meningitidis by the long pentraxin PTX3 and its role as an endogenous adjuvant

PLoS One. 2015 Mar 18;10(3):e0120807. doi: 10.1371/journal.pone.0120807. eCollection 2015.

Authors

Affiliations

¹ Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano (Milan), Italy.
² Novartis Vaccines and Diagnostics Research Center, Siena, Italy.
³ Unidad de Investigación. Hospital Clínico Universitario, Valladolid, Spain.
⁴ Metchnikoff Laboratory, University of Messina, Messina, Italy.
⁵ Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano (Milan), Italy; Humanitas University, Rozzano (Milan), Italy.

Abstract

Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / deficiency
Adjuvants, Immunologic / genetics*
Animals
Animals, Newborn
Antibodies, Bacterial / biosynthesis*
Antibodies, Bacterial / immunology
Antigens, Bacterial / genetics
Antigens, Bacterial / immunology*
Bacterial Load / drug effects
C-Reactive Protein / administration & dosage
C-Reactive Protein / deficiency
C-Reactive Protein / genetics
C-Reactive Protein / immunology*
Female
Gene Expression
Immunity, Humoral / drug effects
Immunity, Innate / drug effects
Male
Meningitis, Meningococcal / immunology
Meningitis, Meningococcal / prevention & control*
Meningitis, Meningococcal / virology
Meningococcal Vaccines / administration & dosage
Meningococcal Vaccines / genetics
Meningococcal Vaccines / immunology*
Mice
Mice, Knockout
Neisseria meningitidis / drug effects
Neisseria meningitidis / genetics
Neisseria meningitidis / immunology*
Ovalbumin / administration & dosage
Rats
Rats, Wistar
Serum Amyloid P-Component / administration & dosage
Serum Amyloid P-Component / deficiency
Serum Amyloid P-Component / genetics
Serum Amyloid P-Component / immunology*
Vaccination

Substances

Adjuvants, Immunologic
Antibodies, Bacterial
Antigens, Bacterial
Meningococcal Vaccines
Serum Amyloid P-Component
PTX3 protein
Ovalbumin
C-Reactive Protein

Grants and funding

BB and AM were founded by the European Research Council (ERC project HIIS) and by the European Commission (FP7-HEALTH-2011-ADITEC-280873). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.