Vaccine 27S (2009) B78–B89 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Meningococcal interactions with the host Etienne Carbonnelle a,1,2 , Darryl J. Hill c,1 , Philippe Morand a,2 , Natalie J. Griffiths c , Sandrine Bourdoulous b , Isabel Murillo c , Xavier Nassif a,2 , Mumtaz Virji c,∗ a INSERM, unité 570, Université Paris Descartes, Faculté de Médecine, 156 rue de Vaugirard, 75015 Paris, France b Institut Cochin, Département de Biologie Cellulaire, INSERM, Unité 567, CNRS, UMR8104, Université Paris Descartes, 22 rue Méchain, 75014 Paris, France c Department of Cellular and Molecular Medicine, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK article info Keywords: Adhesion Receptors Pathogenic mechanisms abstract Neisseria meningitidis interacts with host tissues through hierarchical, concerted and co-ordinated actions of a number of adhesins; many of which undergo antigenic and phase variation, a strategy that helps immune evasion. Three major structures, pili, Opa and Opc predominantly influence bacterial adhe- sion to host cells. Pili and Opa proteins also determine host and tissue specificity while Opa and Opc facilitate efficient cellular invasion. Recent studies have also implied a role of certain adhesin–receptor pairs in determining increased host susceptibility to infection. This chapter examines our current knowl- edge of meningococcal adhesion and invasion mechanisms particularly related to human epithelial and endothelial cells which are of primary importance in the disease process. © 2009 Elsevier Ltd. All rights reserved. 1. Introduction Neisseria meningitidis has evolved attributes that generally enable harmless colonisation of the human nasopharynx, its only known niche; and in most disease cases, asymptomatic colonisa- tion of the nasopharynx precedes infection. Colonisation itself is achieved via versatile and dynamic adhesion and immune eva- sion mechanisms. Whilst antigenic and phase variations of surface structures, including the adhesins, enable bacteria to avoid immune detection, adhesion is maintained through redundancy, i.e. the expression of multiple adhesins, which also aids in colonisation of distinct niches. Although generally regarded as an extracel- lular pathogen, in vitro studies have shown that N. meningitidis entry into cultured human cells can occur via several distinct receptor–adhesin interactions [1–6]. Studies using nasopharyn- geal epithelial organ cultures have also shown that meningococci are able to invade these tissues [8]. In addition, although not clearly demonstrated, meningococcal intracellular location has been implied within mucosal epithelial cells in one study that examined tonsillar biopsies in which meningococci were observed beneath epithelial surfaces [7]. Whether intracellular location in inflamed tissues often used for these investigations represents ‘the norm’ needs to be considered. Studies reported below suggest that ∗ Corresponding author. Tel.: +44 0 117 33 12035; fax: +44 0 117 33 12035. E-mail addresses: xavier.nassif@inserm.fr (X. Nassif), m.virji@bristol.ac.uk (M. Virji). 1 These authors have equally contributed to the work. 2 Tel.: +33 1 40 61 56 78; fax: +33 1 40 61 55 92. inflammatory conditions of the host may influence the balance of the bacteria–host relationship that can change from large surface location to significant cellular penetration. Nonetheless, even low levels of internalisation in a healthy host could benefit bacterial sur- vival through evasion of host phagocytic and antibody/complement mediated killing mechanisms. Internalisation may also provide access to a new source of nutrients and enable bacteria to interfere with host cell functions including innate response to the bacte- rial presence. While in vitro studies have helped unravel some of the complexities of meningococcal interactions with its unique niche, this specificity has prevented the use of animals as mod- els and our understanding of in vivo situations remains unclear. To cause disease, the bacterium enters systemic circulation and mul- tiplies within the host. For this, it requires a “permissive” often immunocompromised host [9]. During the passage across vascular endothelial and the blood–brain/blood–csf barriers, meningococci encounter additional human cells and serum factors with which they interact, often displaying specificity [10]. Since colonisation is the normal state of existence for meningococci, it may be surmised that the bacterial attributes which enable colonisation also aid their dissemination throughout the body. The major adhesins of N. meningitidis include the polymeric pili and the outer membrane opacity proteins, Opa and Opc [1,2,6,11,12]. In addition, a number of other adhesins have been recently iden- tified (Table 1). There is a hierarchy in the utility of adhesins in the context of bacterial phenotype and location. Bacterial capsules tend to be highly hydrated and whilst it is suggested that they may help protect some air-borne bacterial species from desicca- tion, substantiation of this notion is required for N. meningitidis [13,14]. Interestingly, a significant number of mucosal N. meningi- 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.04.069