Exposure to <em>Candida albicans</em> Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis

<div><h3>Background</h3><p>Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of <em>C. albicans</em> in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis.</p> <h3>Methodology</h3><p>Chronic SCW arthritis was induced by repeated injection with <em>Streptococcus pyogenes</em> (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of <em>C. albican</em>s 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.</p> <h3>Principal Findings</h3><p>Intra-articular injection of either Zymosan A or <em>C. albicans</em> 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 <em>C. albicans</em> during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to <em>C. albicans</em> led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORγT. Moreover, the <em>C. albicans</em>-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-γ.</p> <h3>Conclusion</h3><p>This study clearly shows that minute amounts of fungal components, like <em>C. albicans</em>, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype.</p> </div>