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Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- 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.<br />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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....482f3169e8a54e29800470b5acee0008