A6.4 Induction of TH2 cells and eosinophil by infection with nippostrongylus brasiliensis protects against rheumatoid arthritis. (31st January 2014) - Chen, Zhu
Abstract : Background and Objective: Infection with helminth triggers strong Th2 immune response, which modulates the development of systemic autoimmune diseases. The aim of this study was to investigate whether infection with Nippostrongylus brasiliensis influence rheumatoid arthritis development as well as the molecular mechanism from Th2 and eosinophil cells in this effect. Materials and Methods: 5 to 7 weeks old human TNF transgenic (hTNFtg) mice were infected with Nippostrongylus brasiliensis subcutaneously. Moreover, wild-type, IL-4 -/- IL-13 -/- and CD4-Cre IL-4 -/- IL-13 -/ mice were infected with Nippostrongylus brasiliensis subcutaneously 6 days before induction of experimental arthritis through injection of 150 µl K/BxN serum intraperitoneally. Clinical arthritis score and histomorphometric analysis in the inflammatory hind paw were evaluated. Results: Infection with Nippostrongylus brasiliensis alleviated spontaneous chronic arthritis in hTNFtg mice accompanied with a reduction of the systemic and local bone loss. Moreover, wild-type and CD4cre IL-4 -/- IL-13 -/ mice infected with Nippostrongylus brasiliensis have a reduction of the arthritis score whereas arthritis in IL-4 -/- IL-13 -/- mice with infection remained comparable to the non-infected control mice. Histomorphometric analyses revealed that inflammation area and bone erosion were decreased in wild-type and CD4cre IL-4 -/- IL-13 -/ mice with infection compared with IL-4 -/- IL-13 -/- or noninfected wild-type control. Consistently, osteoclast marker such as Trap, RANK and CathepsinK mRNA expression levels in the inflammatory joint were lower in wild-type mice with infection than control. In order to define the role of eosinophil, induction of K/BxN serum transfer arthritis in delta-dblGATA mice was performed. Interestingly genetically lack of eosinophil showed increased inflammation and bone erosion than wild-type control. Conclusions: Infection with Nippostrongylus brasiliensis significantly alleviated bone erosion in experimental arthritis models, which is dependent of IL-4 and IL-13. In addition, eosinophils might play a crucial role in arthritis protection induced by Nippostrongylus brasiliensis infection.