Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia

Journal of Neuroinflammation

Denis Grandgirard¹  Lucy J. Hathaway¹  Stephen L. Leib¹  Asparouh I. Iliev²  Sabrina Hupp²  Timothy J. Mitchell³ 

[1] 0000 0001 0726 5157, grid.5734.5, Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010, Bern, Switzerland;0000 0001 0726 5157, grid.5734.5, Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012, Bern, Switzerland;0000 0004 1936 7486, grid.6572.6, Institute of Microbiology and Infection, College of Medical and Dental Sciences, Biosciences Building, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK;

关键词: Microglia;    Bacterial capsule;    Pneumolysin;    Streptococcus pneumoniae;    Meningitis;   

DOI  :  10.1186/s12974-019-1491-7

来源: publisher

【 摘 要 】

BackgroundStreptococcus pneumoniae is the cause of a highly lethal form of meningitis in humans. Microglial cells in the brain represent the first line of defense against pathogens, and they participate in the inflammatory response. The cholesterol-dependent cytolysin pneumolysin and the bacterial capsule are key pathogenic factors, known to exacerbate the course of pneumococcal meningitis.MethodsWe utilized live imaging and immunostaining of glial cells in dissociated and acute brain slice cultures to study the effect of pneumococcal factors, including the cholesterol-dependent cytolysin pneumolysin and the pneumococcal capsule, on microglial motility and taxis.ResultsIn brain tissue, primary microglia cells showed an enhanced response towards lysates from bacteria lacking capsules and pneumolysin as they moved rapidly to areas with an abundance of bacterial factors. The presence of bacterial capsules and pneumolysin cumulatively inhibited microglial taxis. In mixed cultures of astrocytes and microglia, the motility of microglia was inhibited by capsular components within minutes after exposure. The reduced motility was partially reversed by mannan, a mannose receptor inhibitor. The effects on microglia were not mediated by astrocytes because pure microglial cells responded to various pneumococcal lysates similarly with distinct cell shape changes as seen in mixed cultures.ConclusionsOur data indicate that microglia possess the capacity for a very agile response towards bacterial pathogens, but key pathogenic factors, such as pneumococcal capsules and pneumolysin, inhibited this response shortly after a bacterial challenge. Furthermore, we demonstrate for the first time that the bacterial capsule affects cellular behaviors such as motility and taxis.

【 授权许可】

CC BY