The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis

Hannah E. Jones, Jessica Strid, Mohamed Osman, Heli Uronen-Hansson, Garth Dixon, Nigel Klein, Simon Y C Wong, Robin E. Callard

Research output: Contribution to journalArticle

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Abstract

Phagocytosis of microbial pathogens is essential for the host immune response to infection. Our previous work has shown that lipooligosaccharide (LOS) expression on the surface of Neisseria meningitidis (Nm) is essential for phagocytosis, but the receptor involved remained unclear. In this study, we show that human CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are phagocytic receptors for Nm as illustrated by the capacity of CR3- and CR4-transfected Chinese hamster ovary (CHO) cells to facilitate Nm uptake. A CR3-signalling mutant failed to internalize Nm, showing that the ability of CR3 to signal is essential for phagocytosis. Internalization of Nm by CR3-transfected CHO cells could be inhibited by the presence of CR3-specific antibodies. Furthermore, dendritic cells from leukocyte adhesion deficiency-1 patients, who have diminished expression of ß2 integrins, showed markedly reduced phagocytosis of Nm. The CR3-mediated phagocytosis required the presence of lipopolysaccharide-binding protein (LBP). Furthermore, the expression of LOS by Nm was essential for LBP binding and phagocytosis via CR3. These results reveal a critical role of CR3 and LBP in the phagocytosis of Nm and provide important insights into the initial interaction meningococci have with the immune system.
Original languageEnglish
Pages (from-to)1634-1645
Number of pages12
JournalCellular Microbiology
Volume10
Issue number8
Early online date7 Apr 2008
DOIs
Publication statusPublished - Aug 2008

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CD18 Antigens
Neisseria meningitidis
Phagocytosis
Cricetulus
Ovary
lipopolysaccharide-binding protein
Protein Binding
Cell Adhesion
Integrins
Dendritic Cells
Immune System

Cite this

Jones, H. E., Strid, J., Osman, M., Uronen-Hansson, H., Dixon, G., Klein, N., ... Callard, R. E. (2008). The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis. Cellular Microbiology, 10(8), 1634-1645. https://doi.org/10.1111/j.1462-5822.2008.01154.x

The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis. / Jones, Hannah E.; Strid, Jessica; Osman, Mohamed; Uronen-Hansson, Heli; Dixon, Garth; Klein, Nigel; Wong, Simon Y C; Callard, Robin E.

In: Cellular Microbiology, Vol. 10, No. 8, 08.2008, p. 1634-1645.

Research output: Contribution to journalArticle

Jones, HE, Strid, J, Osman, M, Uronen-Hansson, H, Dixon, G, Klein, N, Wong, SYC & Callard, RE 2008, 'The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis', Cellular Microbiology, vol. 10, no. 8, pp. 1634-1645. https://doi.org/10.1111/j.1462-5822.2008.01154.x
Jones, Hannah E. ; Strid, Jessica ; Osman, Mohamed ; Uronen-Hansson, Heli ; Dixon, Garth ; Klein, Nigel ; Wong, Simon Y C ; Callard, Robin E. / The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis. In: Cellular Microbiology. 2008 ; Vol. 10, No. 8. pp. 1634-1645.
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