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Type: Journal article
Title: Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition
Author: Harris, P.
McNamara, J.
Paterson, D.
Harris, P.
McNamara, J.
Lye, D.
Davis, J.
Tong, S.
Davis, J.
Bernard, L.
Cheng, A.
Cheng, A.
Doi, Y.
Fowler, V.
Kaye, K.
Leibovici, L.
Leibovici, L.
Lipman, J.
Lipman, J.
Lipman, J.
et al.
Citation: Clinical Microbiology and Infection, 2017; 23(8):533-541
Publisher: Elsevier
Issue Date: 2017
ISSN: 1198-743X
Statement of
P.N.A.Harris, J.F.McNamara, D.C.Lye, J.S.Davis, L.Bernard, A.C.Cheng, Y.Doi, V.G.FowlerJr., K.S.Kaye, L.Leibovici, J.Lipman, M.J.Llewelyn, S.Munoz-Price, M.Paul, A.Y.Peleg, J.Rodríguez-Baño, B.A.Rogers, H.Seifert, V.Thamlikitkul, G.Thwaites, S.Y.C.Tong, J.Turnidge, R.Utili, S.A.R.Webb, D.L.Paterson
Abstract: Objective: To examine if the protective effect of parasite infection on experimental autoimmune encephalomyelitis (EAE) was due to interleukin (IL)-5, a cytokine produced by a type-2 response that induces eosinophilia. We hypothesize that, in parasite infections, IL-5 also promotes expansion of antigen-specific T regulatory cells that control autoimmunity. Methods: Nippostrongylus brasiliensis larvae were used to infect Lewis rats prior to induction of EAE by myelin basic protein. Animals were sham treated, or given blocking monoclonal antibodies to interleukin 4 or 5 or to deplete CD25+ T cells. Reactivity of CD4+CD25+ T regulatory cells from these animals was examined. Results: Parasite-infected hosts had reduced severity and length of EAE. The beneficial effect of parasitic infection was abolished with an anti-IL-5 or an anti-CD25 monoclonal antibody (mAb), but not anti-IL-4 mAb. Parasite-infected animals with EAE developed antigen-specific CD4+CD25+ T regulatory cells earlier than EAE controls and these expressed more Il5ra than controls. Treatment with IL-5 also reduced the severity of EAE and induced Il5ra expressing CD4+CD25+ T regulatory cells. Interpretation: The results of this study suggested that IL-5 produced by the type-2 inflammatory response to parasite infection promoted induction of autoantigen-specific CD25+Il5ra+ T regulatory cells that reduced the severity of autoimmunity. Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites.
Keywords: Antibiotic therapy; Bacteraemia; Bacterial infections; Clinical trials; Treatment outcome
Rights: © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
RMID: 0030063025
DOI: 10.1016/j.cmi.2016.10.023
Grant ID:
Appears in Collections:Molecular and Biomedical Science publications

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