Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site

ABSTRACT Plasmodium sporozoites are injected into the skin as mosquitoes probe for blood. From here, they migrate through the dermis to find blood vessels which they enter in order to be rapidly carried to the liver, where they invade hepatocytes and develop into the next life cycle stage, the exoer...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yevel Flores-Garcia, Gibran Nasir, Christine S. Hopp, Christian Munoz, Amanda E. Balaban, Fidel Zavala, Photini Sinnis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	antibodies malaria preerythrocytic skin sporozoites vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7c9212496e404739bb981fe60cff840c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7c9212496e404739bb981fe60cff840c
record_format	dspace
spelling	oai:doaj.org-article:7c9212496e404739bb981fe60cff840c2021-11-15T15:52:19ZAntibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site10.1128/mBio.02194-182150-7511https://doaj.org/article/7c9212496e404739bb981fe60cff840c2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02194-18https://doaj.org/toc/2150-7511ABSTRACT Plasmodium sporozoites are injected into the skin as mosquitoes probe for blood. From here, they migrate through the dermis to find blood vessels which they enter in order to be rapidly carried to the liver, where they invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic stage. Once sporozoites enter the blood circulation, they are found in hepatocytes within minutes. In contrast, sporozoite exit from the inoculation site resembles a slow trickle and occurs over several hours. Thus, sporozoites spend the majority of their extracellular time at the inoculation site, raising the hypothesis that this is when the malarial parasite is most vulnerable to antibody-mediated destruction. Here, we investigate this hypothesis and demonstrate that the neutralizing capacity of circulating antibodies is greater at the inoculation site than in the blood circulation. Furthermore, these antibodies are working, at least in part, by impacting sporozoite motility at the inoculation site. Using actively and passively immunized mice, we found that most parasites are either immobilized at the site of injection or display reduced motility, particularly in their net displacement. We also found that antibodies severely impair the entry of sporozoites into the bloodstream. Overall, our data suggest that antibodies targeting the migratory sporozoite exert a large proportion of their protective effect at the inoculation site. IMPORTANCE Studies in experimental animal models and humans have shown that antibodies against Plasmodium sporozoites abolish parasite infectivity and provide sterile immunity. While it is well documented that these antibodies can be induced after immunization with attenuated parasites or subunit vaccines, the mechanisms by and location in which they neutralize parasites have not been fully elucidated. Here, we report studies indicating that these antibodies display a significant portion of their protective effect in the skin after injection of sporozoites and that one mechanism by which they work is by impairing sporozoite motility, thus diminishing their ability to reach blood vessels. These results suggest that immune protection against malaria begins at the earliest stages of parasite infection and emphasize the need of performing parasite challenge in the skin for the evaluation of protective immunity.Yevel Flores-GarciaGibran NasirChristine S. HoppChristian MunozAmanda E. BalabanFidel ZavalaPhotini SinnisAmerican Society for MicrobiologyarticleantibodiesmalariapreerythrocyticskinsporozoitesvaccineMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibodies malaria preerythrocytic skin sporozoites vaccine Microbiology QR1-502
spellingShingle	antibodies malaria preerythrocytic skin sporozoites vaccine Microbiology QR1-502 Yevel Flores-Garcia Gibran Nasir Christine S. Hopp Christian Munoz Amanda E. Balaban Fidel Zavala Photini Sinnis Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
description	ABSTRACT Plasmodium sporozoites are injected into the skin as mosquitoes probe for blood. From here, they migrate through the dermis to find blood vessels which they enter in order to be rapidly carried to the liver, where they invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic stage. Once sporozoites enter the blood circulation, they are found in hepatocytes within minutes. In contrast, sporozoite exit from the inoculation site resembles a slow trickle and occurs over several hours. Thus, sporozoites spend the majority of their extracellular time at the inoculation site, raising the hypothesis that this is when the malarial parasite is most vulnerable to antibody-mediated destruction. Here, we investigate this hypothesis and demonstrate that the neutralizing capacity of circulating antibodies is greater at the inoculation site than in the blood circulation. Furthermore, these antibodies are working, at least in part, by impacting sporozoite motility at the inoculation site. Using actively and passively immunized mice, we found that most parasites are either immobilized at the site of injection or display reduced motility, particularly in their net displacement. We also found that antibodies severely impair the entry of sporozoites into the bloodstream. Overall, our data suggest that antibodies targeting the migratory sporozoite exert a large proportion of their protective effect at the inoculation site. IMPORTANCE Studies in experimental animal models and humans have shown that antibodies against Plasmodium sporozoites abolish parasite infectivity and provide sterile immunity. While it is well documented that these antibodies can be induced after immunization with attenuated parasites or subunit vaccines, the mechanisms by and location in which they neutralize parasites have not been fully elucidated. Here, we report studies indicating that these antibodies display a significant portion of their protective effect in the skin after injection of sporozoites and that one mechanism by which they work is by impairing sporozoite motility, thus diminishing their ability to reach blood vessels. These results suggest that immune protection against malaria begins at the earliest stages of parasite infection and emphasize the need of performing parasite challenge in the skin for the evaluation of protective immunity.
format	article
author	Yevel Flores-Garcia Gibran Nasir Christine S. Hopp Christian Munoz Amanda E. Balaban Fidel Zavala Photini Sinnis
author_facet	Yevel Flores-Garcia Gibran Nasir Christine S. Hopp Christian Munoz Amanda E. Balaban Fidel Zavala Photini Sinnis
author_sort	Yevel Flores-Garcia
title	Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
title_short	Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
title_full	Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
title_fullStr	Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
title_full_unstemmed	Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site
title_sort	antibody-mediated protection against <italic toggle="yes">plasmodium</italic> sporozoites begins at the dermal inoculation site
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7c9212496e404739bb981fe60cff840c
work_keys_str_mv	AT yevelfloresgarcia antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT gibrannasir antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT christineshopp antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT christianmunoz antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT amandaebalaban antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT fidelzavala antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite AT photinisinnis antibodymediatedprotectionagainstitalictoggleyesplasmodiumitalicsporozoitesbeginsatthedermalinoculationsite
_version_	1718427284390543360

Antibody-Mediated Protection against <italic toggle="yes">Plasmodium</italic> Sporozoites Begins at the Dermal Inoculation Site

Ejemplares similares