Interleukin-4 Receptor Alpha Expressing B Cells Are Essential to Down-Modulate Host Granulomatous Inflammation During Schistosomasis

Front Immunol. 2018 Dec 18:9:2928. doi: 10.3389/fimmu.2018.02928. eCollection 2018.


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-4Rα-expressing B cells is still unknown. To address this, we examined B cell-specific IL-4Rα-deficient (mb1creIL-4Rα-/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-4Rα-expressing B cells were more susceptible to acute schistosomiasis than B cell-deficient (μMT) mice, succumbing to infection at the acute stage whereas μMT mice survived until the chronic stage. An S. mansoni egg challenge model demonstrated that deleting IL-4Rα 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-4Rα-expressing B cells in mb1creIL-4Rα-/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-4Rα-expressing B cells in particular down-modulate the deleterious egg-driven tissue granulomatous inflammation to enable host survival during schistosomiasis in mice.

Keywords: B cells; IL-4RA; chronic infection; pathology; schistosomiais.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation / immunology*
  • Inflammation / mortality
  • Inflammation / parasitology
  • Intestines / immunology
  • Intestines / parasitology
  • Intestines / pathology
  • Liver / immunology
  • Liver / parasitology
  • Liver / pathology
  • Lung / immunology
  • Lung / parasitology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Schistosoma mansoni / immunology*
  • Schistosoma mansoni / pathogenicity
  • Schistosomiasis mansoni / immunology*
  • Schistosomiasis mansoni / mortality
  • Schistosomiasis mansoni / parasitology


  • Il4ra protein, mouse
  • Receptors, Cell Surface