Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites
العنوان: | Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites |
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المؤلفون: | P. Mark Hogarth, Damien R. Drew, Bruce D. Wines, Kiprotich Chelimo, Liriye Kurtovic, Anton Cozijnsen, Michelle J. Boyle, Daniel L Marshall, Gaoqian Feng, Jo-Anne Chan, James W. Kazura, Philippe Boeuf, Arlene E. Dent, Geoffrey I. McFadden, Sandra Chishimba, James G. Beeson, Vanessa Mollard |
المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) |
بيانات النشر: | Nature Publishing Group UK, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Male, Neutrophils, THP-1 Cells, General Physics and Astronomy, Antibodies, Protozoan, Monocytes, 0302 clinical medicine, Child, Multidisciplinary, biology, Middle Aged, Circumsporozoite protein, Sporozoites, Infectious diseases, Female, Antibody, Adult, medicine.drug_class, Science, Plasmodium falciparum, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Article, Antibodies, 03 medical and health sciences, Young Adult, Phagocytosis, Immunity, parasitic diseases, Malaria Vaccines, medicine, Humans, Opsonin, Aged, Receptors, IgG, General Chemistry, biochemical phenomena, metabolism, and nutrition, Translational research, medicine.disease, biology.organism_classification, Kenya, Immunity, Humoral, Malaria, 030104 developmental biology, Humoral immunity, Immunology, biology.protein, 030215 immunology, Parasite host response |
الوصف: | A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy. Antibodies plays critical roles in the adaptive immune response to infectious agents including malaria. Here the authors defined antibody interactions with -Fcγ-receptors expressed on immune cells with sporozoites of Plasmodium falciparum, and identified specific target epitopes of antibodies. |
اللغة: | English |
تدمد: | 2041-1723 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::482f3169e8a54e29800470b5acee0008 http://europepmc.org/articles/PMC7979888 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....482f3169e8a54e29800470b5acee0008 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20411723 |
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