Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis

Debra J. Taxman, Karen V. Swanson, Peter M. Broglie, Haitao Wen, Elizabeth Holley-Guthrie, Max Tze Han Huang, Justin B. Callaway, Tim K. Eitas, Joseph A. Duncan, Jenny P.Y. Ting

Research output: Contribution to journalArticle

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Abstract

The interleukin (IL)-1β-processing inflammasome has recently been identified as a target for pathogenic evasion of the inflammatory response by a number of bacteria and viruses. We postulated that the periodontal pathogen, Porphyromonas gingivalis may suppress the inflammasome as a mechanism for its low immunogenicity and pathogenic synergy with other, more highly immunogenic periodontal bacteria. Our results show that P. gingivalis lacks signaling capability for the activation of the inflammasome in mouse macrophages. Furthermore, P. gingivalis can suppress inflammasome activation by another periodontal bacterium, Fusobacterium nucleatum. This repression affects IL-1β processing, as well as other inflammasome-mediated processes, including IL-18 processing and cell death, in both human and mouse macrophages. F. nucleatum activates IL-1β processing through the Nlrp3 inflammasome; however, P. gingivalis repression is not mediated through reduced levels of inflammasome components. P. gingivalis can repress Nlrp3 inflammasome activation by Escherichia coli, and by danger-associated molecular patterns and pattern-associated molecular patterns that mediate activation through endocytosis. However, P. gingivalis does not suppress Nlrp3 inflammasome activation by ATP or nigericin. This suggests that P. gingivalis may preferentially suppress endocytic pathways toward inflammasome activation. To directly test whether P. gingivalis infection affects endocytosis, we assessed the uptake of fluorescent particles in the presence or absence of P. gingivalis. Our results show that P. gingivalis limits both the number of cells taking up beads and the number of beads taken up for bead-positive cells. These results provide a novel mechanism of pathogen-mediated inflammasome inhibition through the suppression of endocytosis.

Original languageEnglish (US)
Pages (from-to)32791-32799
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number39
DOIs
StatePublished - Sep 21 2012

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Inflammasomes
Porphyromonas gingivalis
Endocytosis
Chemical activation
Interleukin-1
Fusobacterium nucleatum
Bacteria
Macrophages
Pathogens
Processing
Nigericin
Interleukin-18
Cell death
Viruses
Escherichia coli
Cell Death
Cell Count
Adenosine Triphosphate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Taxman, D. J., Swanson, K. V., Broglie, P. M., Wen, H., Holley-Guthrie, E., Huang, M. T. H., ... Ting, J. P. Y. (2012). Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis. Journal of Biological Chemistry, 287(39), 32791-32799. https://doi.org/10.1074/jbc.M112.401737

Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis. / Taxman, Debra J.; Swanson, Karen V.; Broglie, Peter M.; Wen, Haitao; Holley-Guthrie, Elizabeth; Huang, Max Tze Han; Callaway, Justin B.; Eitas, Tim K.; Duncan, Joseph A.; Ting, Jenny P.Y.

In: Journal of Biological Chemistry, Vol. 287, No. 39, 21.09.2012, p. 32791-32799.

Research output: Contribution to journalArticle

Taxman, DJ, Swanson, KV, Broglie, PM, Wen, H, Holley-Guthrie, E, Huang, MTH, Callaway, JB, Eitas, TK, Duncan, JA & Ting, JPY 2012, 'Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis', Journal of Biological Chemistry, vol. 287, no. 39, pp. 32791-32799. https://doi.org/10.1074/jbc.M112.401737
Taxman, Debra J. ; Swanson, Karen V. ; Broglie, Peter M. ; Wen, Haitao ; Holley-Guthrie, Elizabeth ; Huang, Max Tze Han ; Callaway, Justin B. ; Eitas, Tim K. ; Duncan, Joseph A. ; Ting, Jenny P.Y. / Porphyromonas gingivalis mediates inflammasome repression in polymicrobial cultures through a novel mechanism involving reduced endocytosis. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 39. pp. 32791-32799.
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