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      Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

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          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.

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          Most cited references 62

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                Author and article information

                Cell Rep
                Cell Rep
                Cell reports
                24 October 2016
                4 October 2016
                27 October 2016
                : 17
                : 2
                : 399-412
                [1 ]QIMR Berghofer Medical Research Institute, Royal Brisbane and Women’s Hospital, Brisbane, QLD 4006, Australia
                [2 ]School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
                [3 ]Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
                [4 ]Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia
                [5 ]Institute of Glycomics, Griffith University, Gold Coast, Southport, QLD 4215, Australia
                [6 ]School of Natural Sciences, Griffith University, Nathan, QLD 4111, Australia
                [7 ]Menzies School of Health Research, Darwin, NT 0811, Australia
                [8 ]Charles Darwin University, Darwin, NT 0810, Australia
                [9 ]Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK
                Author notes
                [* ]Correspondence: j.mccarthy@ (J.S.M.), chrise@ (C.R.E.)

                Present address: National Centre for Immunisation Research and Surveillance, Westmead, NSW 2145, Australia


                Present address: Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia


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                This is an open access article under the CC BY-NC-ND license (


                Cell biology


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