title: Human Memory CD4+ T Cell Immune Responses against Giardia lamblia.
abstract: The intestinal protozoan parasite Giardia lamblia may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to Giardia infection, and memory responses may last years. Recently, TH17 responses have been found in three animal studies of Giardia infection. The aim of this study was to characterize the human CD4(+) T cell responses to Giardia. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated in vitro with Giardia lamblia proteins. Production of tumor necrosis factor alpha (TNF-α), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4(+) effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4(+) EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-α, to be significantly elevated in the Giardia-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with Giardia antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4(+) T cell activation and proliferation, to be significantly elevated in the Giardia-exposed individuals. We conclude that symptomatic Giardia infection in humans induces a CD4(+) EM T cell response of which IL-17A production seems to be an important component.
authors.affiliation: National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, University of Bergen, Bergen, Norway christina.saghaug@uib.no.
authors.forename: Christina Skår
authors.identifier: http://orcid.org/0000-0003-0836-7889
authors.initials: CS
authors.lastname: Saghaug
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Sørnes
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Peirasmaki
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Svärd
authors.affiliation: National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Langeland
authors.affiliation: National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Kurt
authors.identifier: http://orcid.org/0000-0002-1466-2326
authors.initials: K
authors.lastname: Hanevik
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016829:Giardia lamblia / Q000276:immunology*; D005873:Giardiasis / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma