Jean Pierre Kambala Mukendi1,2,3, Risa Nakamura1,2,3, Satoshi Uematsu4,5, Shinjiro Hamano6,7,8. 1. Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. 2. Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. 3. The Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. 4. Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka, Japan. 5. Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. 6. Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. shinjiro@nagasaki-u.ac.jp. 7. Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. shinjiro@nagasaki-u.ac.jp. 8. The Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. shinjiro@nagasaki-u.ac.jp.
Abstract
BACKGROUND: Schistosomes are trematode worms that dwell in their definitive host's blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice. METHODS: The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infected mice. RESULTS: Worms from IL-33-/- and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33-/- and WT mice differed only slightly. At 6 wpi, IL-33-/- mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33-/- and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues. CONCLUSIONS: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.
BACKGROUND: Schistosomes are trematode worms that dwell in their definitive host's blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice. METHODS: The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infectedmice. RESULTS: Worms from IL-33-/- and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33-/- and WT mice differed only slightly. At 6 wpi, IL-33-/- mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33-/- and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues. CONCLUSIONS: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.
Authors: Gabriele Schramm; Franco H Falcone; Achim Gronow; Karin Haisch; Uwe Mamat; Michael J Doenhoff; Guilherme Oliveira; Jürgen Galle; Clemens A Dahinden; Helmut Haas Journal: J Biol Chem Date: 2003-03-06 Impact factor: 5.157
Authors: Luke F Pennington; Abdulaziz Alouffi; Evaristus C Mbanefo; Debalina Ray; David M Heery; Theodore S Jardetzky; Michael H Hsieh; Franco H Falcone Journal: Infect Immun Date: 2017-11-17 Impact factor: 3.441
Authors: Bart Everts; Georgia Perona-Wright; Hermelijn H Smits; Cornelis H Hokke; Alwin J van der Ham; Colin M Fitzsimmons; Michael J Doenhoff; Jürgen van der Bosch; Katja Mohrs; Helmut Haas; Markus Mohrs; Maria Yazdanbakhsh; Gabriele Schramm Journal: J Exp Med Date: 2009-07-27 Impact factor: 14.307