Host IFN-γ is dispensable for anti-arthritic effects of Plasmodium yoelii 17XNL in mouse collagen-induced arthritis.

We previously reported that Plasmodium yoelii 17XNL (Py) protected mice from collagen-induced arthritis (CIA). However, the host factors required for this protection are not fully understood. As interferon-gamma (IFN-γ) is often induced by protozoan infections and is also known as an anti-arthritic cytokine in CIA, we here investigated the requirement of IFN-γ for the anti-arthritic effects of Py infection. CIA was induced by immunization with collagen type II (CII) emulsified with Freund's complete adjuvant in IFN-γ knockout (IFN-γKO) and wild-type (WT) mice. At 2-week post-immunization, mice were inoculated with Py. In addition to evaluation of arthritis severity, serum levels of anti-CII IgG antibodies and splenic cytokine production were determined. In IFN-γKO mice, Py infection suppressed CIA development and downregulated pro-arthritic cytokines (IL-17A and TNF-α) during the period of parasitemia. However, a marked rebound of arthritis occurred after parasite clearance, associated with a surge in serum anti-CII IgG2a levels. Our findings demonstrate that host IFN-γ is not required for the initial suppression of CIA by Py infection during parasitemia. The subsequent rebound of arthritic symptoms after parasite clearance in the IFN-γKO mice was associated with a surge in anti-CII IgG, particularly the IgG2a subclass.