Dataset Information

Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

ABSTRACT:

Background

Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis.

Methodology

Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry.

Principal findings

Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and ROR?T. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-?.

Conclusion

This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype.

SUBMITTER: Marijnissen RJ

PROVIDER: S-EPMC3373564 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

Marijnissen Renoud J RJ Koenders Marije I MI van de Veerdonk Frank L FL Dulos John J Netea Mihai G MG Boots Annemieke M H AM Joosten Leo A B LA van den Berg Wim B WB

PloS one 20120612 6

<h4>Background</h4>Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis.<h4>Methodology</h4>Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination ...[more]

PMID: 22719976

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Project description:Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)?, IL-1? and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway.We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide ?-defensin 2 (BD2) in saliva.Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P?=?0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P?=?0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P?=?0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P?=?0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P?=?0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P?=?0.70).RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a strongly Th17-dependent opportunistic pathogen, despite an overall elevated baseline production of IL-17A.

Dataset Information

Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

Background

Methodology

Principal findings

Conclusion

Publications

Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

Similar Datasets

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