The role of the collectins in determining innate susceptibility to meningococcal disease
Dr Dominic Jack, Dr Nigel Klein, Professor Robert Read
- Start Date:
01 January 2002
University of Sheffield, Sheffield, UK
The collectins are a family of innate immune proteins which share structural features and some functions. It has been suggested that deficiency of the human serum collectin, mannose-binding lectin (MBL), predisposes individuals to infection by Neisseria meningitidis. Two other collectins, lung surfactant proteins (SP)-A and -D, are found in humans at epithelial surfaces including the respiratory mucosa. Levels of both are inducible and under genetic control, and we have demonstrated that SP-D binds to N. meningitidis. MBL and SP-D appear to bind to opacity associated protein and porin B, which are both involved in the interaction of Neisseria with host cells. SP-A binds to related proteins on Haemophilus influenzae. We propose to investigate the interaction of the collectins with N. meningitidis, because these proteins are present throughout the cycle of colonisation and invasion of the human host, induce a number of immune functions critical in disease pathogenesis and are highly variable between different humans. This information will be critical in identifying who is more susceptible to meningococcal infection and why, which will lead to better targeting of vaccine resources and strategies of prevention. We propose to investigate collectin polymorphisms in patients from a Meningitis Research Foundation-funded cohort of meningococcal patients and controls. We will investigate collectin functions and interactions with a nasopharyngeal organ culture system. We will study fundamental collectin functions using an epithelial cell association model and complement activation assays.
Results from this study have been published in scientific journals as follows:
Jack DL, Lee ME, Turner MW, Klein NJ, Read RC,
Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages.
J Leukoc Biol 2005 Mar;77(3):328-36. Epub 2004 Nov 29.
Jack DL, Cole J, Naylor SC, Borrow R, Kaczmarski EB, Klein NJ, Read RC,
Genetic polymorphism of the binding domain of surfactant protein-A2 increases susceptibility to meningococcal disease. Clin Infect Dis 2006 Dec 1;43(11):1426-33. Epub 2006 Oct 31. http://www.journals.uchicago.edu/CID/journal/issues/v43n11/40274/40274.web.pdf