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

Hupp, Sabrina; Grandgirard, Denis; Mitchell, Timothy J.; Leib, Stephen; Hathaway, Lucy Jane; Iliev, Asparouh I. (2019). Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia. Journal of neuroinflammation, 16(1), p. 105. BioMed Central 10.1186/s12974-019-1491-7

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Background Streptococcus 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. Methods We 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. Results In 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. Conclusions Our 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Clinical Microbiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy

UniBE Contributor:

Hupp, Sabrina; Grandgirard, Denis; Leib, Stephen; Hathaway, Lucy Jane and Iliev, Asparouh Iliev

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1742-2094

Publisher:

BioMed Central

Funders:

[4] Swiss National Science Foundation

Projects:

[UNSPECIFIED] Swiss National Fund (SNF) No. 160136 to AII, 170844 to LJH and 162583 to SLL.

Language:

English

Submitter:

Sabrina Hupp

Date Deposited:

17 Jul 2019 10:14

Last Modified:

22 Oct 2019 17:23

Publisher DOI:

10.1186/s12974-019-1491-7

PubMed ID:

31103037

Uncontrolled Keywords:

Bacterial capsule Meningitis Microglia Pneumolysin Streptococcus pneumoniae

BORIS DOI:

10.7892/boris.130787

URI:

https://boris.unibe.ch/id/eprint/130787

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