Schistosome Infection Promotes Osteoclast-Mediated Bone Loss

Author summarySchistosomiasis remains an important public health problem in many countries in tropical and subtropical regions, which affects about 200 million people worldwide, with another 700 million considered at risk of infection. Although the primary cause of pathogenesis of schistosomiasis is the granulomatous inflammatory responses, schistosomiasis patients experience long-term hidden pathologies that remain poorly investigated. Here, we found that schistosome infection resulted in RANKL-associated bone loss. Furthermore, our results indicated that both B cells and CD4(+) T cells, particularly Tfh cell subset, in the peripheral lymphoid tissues are likely to be the important contributors to bone loss through releasing soluble RANKL. In addition, Tfh cells played a sufficient but not necessary role in schistosome infection-induced bone loss. Our findings highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-kappa B (NF-kappa B) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4(+) T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.