title: Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection.
abstract: The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Marcela
authors.initials: M
authors.lastname: Montes de Oca
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Fabian de Labastida
authors.initials: FL
authors.lastname: Rivera
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Amante
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Meru
authors.initials: M
authors.lastname: Sheel
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Faleiro
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; Institute of Glycomics, Griffith University, Gold Coast, Southport, QLD 4215, Australia.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bunn
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Best
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; School of Natural Sciences, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Ng
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Edwards
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Glen M
authors.initials: GM
authors.lastname: Boyle
authors.affiliation: Menzies School of Health Research, Darwin, NT 0811, Australia; Charles Darwin University, Darwin, NT 0810, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Menzies School of Health Research, Darwin, NT 0811, Australia; Charles Darwin University, Darwin, NT 0810, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Menzies School of Health Research, Darwin, NT 0811, Australia; Charles Darwin University, Darwin, NT 0810, Australia.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Loughland
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Burel
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia; School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: j.mccarthy@uq.edu.au.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.affiliation: QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia. Electronic address: chrise@qimr.edu.au.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
mesh_terms: D000977:Antiparasitic Agents / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D064368:Healthy Volunteers; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007370:Interferon Type I / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000977:Antiparasitic Agents; C573415:IFNG protein, human; D007370:Interferon Type I; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD4(+) T cells; Th1 cells; Tr1 cells; immune regulation; malaria; type I interferons