| First Author | Ndlovu H | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 2928 | PubMed ID | 30619289 |
| Mgi Jnum | J:295548 | Mgi Id | MGI:6453951 |
| Doi | 10.3389/fimmu.2018.02928 | Citation | Ndlovu H, et al. (2018) Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis. Front Immunol 9:2928 |
| abstractText | Schistosomiasis (bilharzia) is a parasitic helminth disease that can cause severe inflammatory pathology leading to organ damage in humans. Failure of the host to regulate egg-driven granulomatous inflammation causes host morbidity during chronic infection with Schistosoma mansoni. Although the importance of B cells in regulating pathology during chronic infection has been well defined, the specific contribution of IL-4Ralpha-expressing B cells is still unknown. To address this, we examined B cell-specific IL-4Ralpha-deficient (mb1(cre)IL-4Ralpha(-/lox)) mice in three experimental models of schistosomiasis: high-dose (100 cercariae), low dose (30 cercariae), and a synchronous egg challenge. In the high dose model, we found that mice deficient in IL-4Ralpha-expressing B cells were more susceptible to acute schistosomiasis than B cell-deficient (muMT) mice, succumbing to infection at the acute stage whereas muMT mice survived until the chronic stage. An S. mansoni egg challenge model demonstrated that deleting IL-4Ralpha expression specifically on B cells resulted in increased lung granulomatous pathology, suggesting a role for this B cell subset in controlling granulomatous pathology. In agreement with this, a low dose model of schistosomiasis-which mimics the course of clinical chronic disease-demonstrated that depleting IL-4Ralpha-expressing B cells in mb1(cre)IL-4Ralpha(-/lox) mice considerably impaired the host ability to down-modulate granulomatous inflammation in the liver and gut during chronic schistosomiasis. Taken together, our findings indicate that within the B cell compartment, IL-4Ralpha-expressing B cells in particular down-modulate the deleterious egg-driven tissue granulomatous inflammation to enable host survival during schistosomiasis in mice. |
