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Immunological profiles associated with distinct parasitemic states in volunteers undergoing malaria challenge in Gabon.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
    • نبذة مختصرة :
      Controlled human malaria infection (CHMI) using cryopreserved non-attenuated Plasmodium falciparum sporozoites (PfSPZ) offers a unique opportunity to investigate naturally acquired immunity (NAI). By analyzing blood samples from 5 malaria-naïve European and 20 African adults with lifelong exposure to malaria, before, 5, and 11 days after direct venous inoculation (DVI) with Sanaria R PfSPZ Challenge, we assessed the immunological patterns associated with control of microscopic and submicroscopic parasitemia. All (5/5) European individuals developed parasitemia as defined by thick blood smear (TBS), but 40% (8/20) of the African individuals controlled their parasitemia, and therefore remained thick blood smear-negative (TBS - Africans). In the TBS - Africans, we observed higher baseline frequencies of CD4 + T cells producing interferon-gamma (IFNγ) that significantly decreased 5 days after PfSPZ DVI. The TBS - Africans, which represent individuals with either very strong and rapid blood-stage immunity or with immunity to liver stages, were stratified into subjects with sub-microscopic parasitemia (TBS - PCR + ) or those with possibly sterilizing immunity (TBS - PCR - ). Higher frequencies of IFNγ + TNF + CD8 + γδ T cells at baseline, which later decreased within five days after PfSPZ DVI, were associated with those who remained TBS - PCR - . These findings suggest that naturally acquired immunity is characterized by different cell types that show varying strengths of malaria parasite control. While the high frequencies of antigen responsive IFNγ + CD4 + T cells in peripheral blood keep the blood-stage parasites to a sub-microscopic level, it is the IFNγ + TNF + CD8 + γδ T cells that are associated with either immunity to the liver-stage, or rapid elimination of blood-stage parasites.
      (© 2022. The Author(s).)
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    • Grant Information:
      R01GM9987654 United States NH NIH HHS
    • الرقم المعرف:
      0 (Malaria Vaccines)
      82115-62-6 (Interferon-gamma)
    • الموضوع:
      Date Created: 20220803 Date Completed: 20220805 Latest Revision: 20221014
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC9349185
    • الرقم المعرف:
      10.1038/s41598-022-17725-8
    • الرقم المعرف:
      35922467