Changes in pro inflammatory and regulatory immune responses during controlled human schistosome infection and the development of clinical symptoms
Abstract
Abstract Schistosomiasis is a prevalent helminthiasis, affecting over 230 million people worldwide, with varied, stage specific morbidity. Whilst the Th2 and regulatory immune responses in chronic infection have been relatively well studied, we have little understanding of human immune responses during acute infection. This is despite the initial infective stages being proposed as crucial targets for much-needed vaccine development. Here, we comprehensively map immune responses in male and female single-sex controlled human Schistosoma mansoni infection. Using unbiased, high dimensional techniques we show that human immune responses to male and female single-sex infection are comparable. An early Th1-biased inflammatory response was observed at week 4 post infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. This included expansion of HLA-DR + effector memory T cells, CD38 + monocytes and an increase in serum IFNγ. By week 8 post infection these inflammatory responses were followed by an expansion of Th2 and of regulatory cell subsets, including IL-10 producing CD4 - CD8 - T cells, CD11c + atypical memory B cells and serum IL-10. This study provides immunological insight into the clinical manifestations of acute schistosomiasis, as well as critical context through which to understand the development of immune responses observed in natural infection. One sentence summary Controlled human schistosome infection reveals cellular and cytokine responses to schistosome infection, with early inflammatory responses in symptomatic individuals at week 4 and a balanced Th1, Th2 and regulatory response in all participants by week 8.
Authors 15
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Emma L. Houlder Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Koen A. Stam Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Jan Pieter R. Koopman Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Marion H. König Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Marijke C. C. Langenberg Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Marie-Astrid Hoogerwerf Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Paula Niewold Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Friederike Sonnet Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Jacqueline J. Janse Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Miriam Casacuberta-Partal Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Jeroen C. Sijtsma Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Laura de Bes-Roeleveld Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Yvonne C. M. Kruize Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Maria Yazdanbakhsh Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center; Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Albinusdreef 2, 2333ZA, Leiden, The Netherlands
Leiden University Center for Infectious Diseases, Leiden University Medical Center
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