Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.1207810 on February 25, 2008

Published online before print February 25, 2008
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(Journal of Leukocyte Biology. 2008;83:1100-1110.)
© 2008 by Society for Leukocyte Biology

Human monocytes/macrophages are a target of Neisseria meningitidis Adhesin A (NadA)

Susanna Franzoso*, Cristina Mazzon*, Maryta Sztukowska{dagger}, Paola Cecchini*, Tihana Kasic{ddagger}, Barbara Capecchi§, Regina Tavano* and Emanuele Papini*,1

* Centro Ricerche Biotecnologie Innovative and
{ddagger} Istituto Veneto Medicina Molecolare, Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, Padova, Italy;
{dagger} Rzeszów University of Technology, Faculty of Chemistry, Department of Biochemistry and Biotechnology, Rzeszów, Poland; and
§ Research Centre, Novartis Vaccines and Diagnostics S.r.l., Siena, Italy

1Correspondence: C.R.I.B.I.-University of Padova, Via G. Colombo 3, 35121 Padova, Italy. E-mail: emanuele.papini{at}unipd.it

ABSTRACT

Specific surface proteins of Neisseria meningitidis have been proposed to stimulate leukocytes during tissue invasion and septic shock. In this study, we demonstrate that the adhesin N. meningitidis Adhesin A (NadA) involved in the colonization of the respiratory epithelium by hypervirulent N. meningitidis B strains also binds to and activates human monocytes/macrophages. Expression of NadA on the surface on Escherichia coli does not increase bacterial-monocyte association, but a NadA-positive strain induced a significantly higher amount of TNF-{alpha} and IL-8 compared with the parental NadA-negative strain, suggesting that NadA has an intrinsic stimulatory action on these cells. Consistently, highly pure, soluble NadA{Delta}351–405, a proposed component of an antimeningococcal vaccine, efficiently stimulates monocytes/macrophages to secrete a selected pattern of cytokines and chemotactic factors characterized by high levels of IL-8, IL-6, MCP-1, and MIP-1{alpha} and low levels of the main vasoactive mediators TNF-{alpha} and IL-1. NadA{Delta}351–405 also inhibited monocyte apoptosis and determined its differentiation into a macrophage-like phenotype.

Key Words: adhesion molecule • bacterial infection • inflammation • cytokines • chemokines






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