Affiliation:
1. Department of Clinical Science Faculty of Medicine University of Bergen Bergen Norway
2. Department of Clinical Science Centre of Cancer Biomarkers (CCBIO) University of Bergen Bergen Norway
3. Hematology Section Department of Internal Medicine Helse Bergen Bergen Norway
4. Division of Cancer Medicine Department of Cancer Immunology Oslo University Hospital Oslo Norway
5. Department of Global Public Health and Primary Care Faculty of Medicine Centre for Intervention Science in Maternal and Child Health (CISMAC) Centre for International Health University of Bergen Bergen Norway
6. Department of Biomedicine Faculty of Medicine University of Bergen Bergen Norway
7. Department of Medicine Norwegian National Advisory Unit on Tropical Infectious Diseases Haukeland University Hospital Bergen Norway
Abstract
AbstractEnterotoxigenic Escherichia coli (ETEC) is an important cause of children's and travelers’ diarrhea, with no licensed vaccine. This study aimed to explore the role of cellular immunity in protection against human ETEC infection. Nine volunteers were experimentally infected with ETEC, of which six developed diarrhea. Lymphocytes were collected from peripheral blood buffy coats, before and 3, 5, 6, 7, 10, and 28 days after dose ingestion, and 34 phenotypic and functional markers were examined by mass cytometry. Thirty‐three cell populations, derived by manually merging 139 cell clusters from the X‐shift unsupervised clustering algorithm, were analyzed. Initially, the diarrhea group responded with increased CD56dim CD16+ natural killer cells, dendritic cells tended to rise, and mucosal‐associated invariant T cells decreased. On day 5‐7, an increase in plasmablasts was paralleled by a consistent rise in CD4+ Th17‐like effector memory and regulatory cell subsets. CD4+ Th17‐like central memory cells peaked on day 10. All Th17‐like cell populations showed increased expression of activation, gut‐homing, and proliferation markers. Interestingly, in the nondiarrhea group, these same CD4+ Th17‐like cell populations expanded earlier, normalizing around day 7. Earlier development of these CD4+ Th17‐like cell populations in the nondiarrhea group may suggest a recall response and a potential role in controlling ETEC infections.
Subject
Immunology,Immunology and Allergy