Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin

Author(s):Show less -

Aliprandini, Eduardo ^[1] ; Tavares, Joana ^{[2, 3]} ; Panatieri, Raquel Hoffmann ^{[1, 4]} ; Thiberge, Sabine ^{[1, 5]} ; Yamamoto, Marcio Massao ^[4] ; Silvie, Olivier ^[6] ; Ishino, Tomoko ^[7] ; Yuda, Masao ^[8] ; Dartevelle, Sylvie ^[9] ; Traincard, Francois ^[9] ; Boscardin, Silvia Beatriz ^[4] ; Amino, Rogerio ^[1]

Affiliation

^[1] Inst Pasteur, Unit Malaria Infect & Immun, Paris - France

^[2] Univ Porto, Inst Invest & Inovacao Saude, Porto - Portugal

^[3] Univ Porto, Inst Biol Mol & Celular, Porto - Portugal

^[4] Univ Sao Paulo, Inst Biomed Sci, Parasitol Dept, Sao Paulo - Brazil

^[5] Inst Pasteur, Ctr Prod Infect Anopheles, Paris - France

^[6] Sorbonne Univ, INSERM, CIMI, CNRS, Paris - France

^[7] Ehime Univ, Dept Mol Parasitol, Matsuyama, Ehime - Japan

^[8] Mie Univ, Dept Med Zool, Sch Med, Tsu, Mie - Japan

^[9] Inst Pasteur, Plateforme Ingn Anticorps, Paris - France

• Document type: Journal article
• Source: NATURE MICROBIOLOGY; v. 3, n. 11, p. 1224-1233, NOV 2018.
• Web of Science Citations: 8

Abstract

The circumsporozoite protein (CSP) is the major surface protein of malaria sporozoites (SPZs), the motile and invasive parasite stage inoculated in the host skin by infected mosquitoes. Antibodies against the central CSP repeats of different plasmodial species are known to block SPZ infectivity(1-5), but the precise mechanism by which these effectors operate is not completely understood. Here, using a rodent Plasmodium yoelii malaria model, we show that sterile protection mediated by anti-P. yoelii CSP humoral immunity depends on the parasite inoculation into the host skin, where antibodies inhibit motility and kill P. yoelii SPZs via a characteristic `dotty death' phenotype. Passive transfer of an anti-repeat monoclonal antibody (mAb) recapitulates the skin inoculation-dependent protection, in a complement- and Fc receptor gamma-independent manner. This purified mAb also decreases motility and, notably, induces the dotty death of P. yoelii SPZs in vitro. Cytotoxicity is species-transcendent since cognate anti-CSP repeat mAbs also kill Plasmodium berghei and Plasmodium falciparum SPZs. mAb cytotoxicity requires the actomyosin motor-dependent translocation and stripping of the protective CSP surface coat, rendering the parasite membrane susceptible to the SPZ poreforming-like protein secreted to wound and traverse the host cell membrane(6). The loss of SPZ fitness caused by anti-P. yoelii CSP repeat antibodies is thus a dynamic process initiated in the host skin where SPZs either stop moving(7), or migrate and traverse cells to progress through the host tissues(7-9) at the eventual expense of their own life. (AU)

• FAPESP's process: 14/50631-0 - Imaging and improvement of immune protection against malaria parasites
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants