Inactive Gingipains from P. gingivalis Selectively Skews T Cells toward a Th17 Phenotype in an IL-6 Dependent Manner

Frontiers in Cellular and Infection Microbiology
Izabela GlowczykJoanna Koziel

Abstract

Gingipain cysteine proteases are considered key virulence factors of Porphyromonas gingivalis. They significantly influence antibacterial and homeostatic functions of macrophages, neutrophils, the complement system, and cytokine networks. Recent data indicate the role of P. gingivalis in T cell differentiation; however, the involvement of gingipains in this process remains elusive. Therefore, the aim of this study was to investigate the contribution of danger signals triggered by the gingipains on the generation of Th17 cells, which play a key role in protection against bacterial diseases but may cause chronic inflammation and bone resorption. To this end we compared the effects of the wild-type strain of P. gingivalis (W83) with its isogenic mutant devoid of gingipain activity (ΔKΔRAB), and bacterial cells pretreated with a highly-specific inhibitor of gingipains activity (KYTs). Antigen presenting cells (APCs), both professional (dendritic cells), and non-professional (gingival keratinocytes), exposed to viable bacteria expressed high amounts of cytokines (IL-6, IL-21, IL-23). These cytokines are reported to either stimulate or balance the Th17-dependent immune response. Surprisingly, cells infected with P. gingivalis devoid ...Continue Reading

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Citations

Nov 9, 2018·Molecular Oral Microbiology·Jeffrey L EbersoleOctavio A Gonzalez
Feb 5, 2021·Journal of Molecular Biology·Ignacio Lunar Silva, Eric Cascales
Aug 19, 2021·Journal of Leukocyte Biology·Yu-Dong XuYong-Qing Yang
Dec 9, 2021·Journal of Periodontal Research·Jianwen DengZejian Li

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Methods Mentioned

BETA
density gradient centrifugation
PCR
PMA
ELISA
flow cytometry
dot blot

Software Mentioned

FCAP Array
FlowJo

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