Contribution of receptors to 'Neisseria meningitidis' interactions with human macrophages

N. meningitidis is a gram-negative human pathogen that invades human cells, evades immune responses and goes on to cause meningococcal disease, sepsis and death. Serogroups B and C are most prevalent in industrialised countries, with over 50% of cases due to serogroup B, which as yet, has no effective vaccine. The work described involved developing methods and adapting effective model systems used throughout this study, and examination of which possible opsonic receptors may be involved in bacterial interactions in the presence of serum. The study revealed the involvement of CD 14 in meningococcal recognition was examined using a number of approaches, including glycosylphosphatidylinositol- (GPI) cleaving enzyme, phosphatidylinositol phospholipase C (PIPLC), appropriate anti-CD14 blocking antibody and CD14 transfectants. Class A scavenger receptor (SR-A) were also found to contribute significantly to meningococcal recognition by human macrophages. This observation was supported by the use of THP-1 monocytic cells; PMA-differentiation resulted in recovery of phagocytosis that could be inhibited with SR-A blocking reagent, Poly I. Immune serum-mediated interactions implicated CR3 and Fcy receptor involvement as well as that of cholesterol-rich lipid rafts. I also examine the role of non-opsonic receptors by using the first viable LPS-deficient strain of N. meningitidis, and note that the lpxA mutant adheres to primary human macrophages more effectively than its parent strain, but internalisation, LAMP-1 incorporation and TNF production were all severely reduced.