Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent

ABSTRACT Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate...

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Autores principales:	Maria L. Simões, Godfree Mlambo, Abhai Tripathi, Yuemei Dong, George Dimopoulos
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Anopheles Plasmodium innate immunity melanization malaria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d90ef7a1a44b48d98090fa7f7968bec7
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spelling	oai:doaj.org-article:d90ef7a1a44b48d98090fa7f7968bec72021-11-15T15:51:51ZImmune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent10.1128/mBio.01631-172150-7511https://doaj.org/article/d90ef7a1a44b48d98090fa7f7968bec72017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01631-17https://doaj.org/toc/2150-7511ABSTRACT Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate immunity factors as agonists or antagonists of malaria parasite infection has been previously determined using specific single Anopheles-Plasmodium species combinations. Here we show that the two C-type lectins CTL4 and CTLMA2 exert differential agonistic and antagonistic regulation of parasite killing in African and South American Anopheles species. The C-type lectins regulate both parasite melanization and lysis through independent mechanisms, and their implication in parasite melanization is dependent on infection intensity rather than mosquito-parasite species combination. We show that the leucine-rich repeat protein LRIM1 acts as an antagonist on the development of Plasmodium ookinetes and as a regulator of oocyst size and sporozoite production in the South American mosquito Anopheles albimanus. Our findings explain the rare observation of human Plasmodium falciparum melanization and define a key factor mediating the poor vector competence of Anopheles albimanus for Plasmodium berghei and Plasmodium falciparum. IMPORTANCE Malaria, one of the world’s deadliest diseases, is caused by Plasmodium parasites that are vectored to humans by the bite of Anopheles mosquitoes. The mosquito’s innate immune system is actively engaged in suppressing Plasmodium infection. Studies on mosquito immunity revealed multiple factors that act as either facilitators or inhibitors of Plasmodium infection, but these findings were mostly based on single Anopheles-Plasmodium species combinations, not taking into account the diversity of mosquito and parasite species. We show that the functions of CTL4 and CTLMA2 have diverged in different vector species and can be both agonistic and antagonistic for Plasmodium infection. Their protection against parasite melanization in Anopheles gambiae is dependent on infection intensity, rather than the mosquito-parasite combination. Importantly, we describe for the first time how LRIM1 plays an essential role in Plasmodium infection of Anopheles albimanus, suggesting it is a key regulator of the poor vector competence of this species.Maria L. SimõesGodfree MlamboAbhai TripathiYuemei DongGeorge DimopoulosAmerican Society for MicrobiologyarticleAnophelesPlasmodiuminnate immunitymelanizationmalariaMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Anopheles Plasmodium innate immunity melanization malaria Microbiology QR1-502
spellingShingle	Anopheles Plasmodium innate immunity melanization malaria Microbiology QR1-502 Maria L. Simões Godfree Mlambo Abhai Tripathi Yuemei Dong George Dimopoulos Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
description	ABSTRACT Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate immunity factors as agonists or antagonists of malaria parasite infection has been previously determined using specific single Anopheles-Plasmodium species combinations. Here we show that the two C-type lectins CTL4 and CTLMA2 exert differential agonistic and antagonistic regulation of parasite killing in African and South American Anopheles species. The C-type lectins regulate both parasite melanization and lysis through independent mechanisms, and their implication in parasite melanization is dependent on infection intensity rather than mosquito-parasite species combination. We show that the leucine-rich repeat protein LRIM1 acts as an antagonist on the development of Plasmodium ookinetes and as a regulator of oocyst size and sporozoite production in the South American mosquito Anopheles albimanus. Our findings explain the rare observation of human Plasmodium falciparum melanization and define a key factor mediating the poor vector competence of Anopheles albimanus for Plasmodium berghei and Plasmodium falciparum. IMPORTANCE Malaria, one of the world’s deadliest diseases, is caused by Plasmodium parasites that are vectored to humans by the bite of Anopheles mosquitoes. The mosquito’s innate immune system is actively engaged in suppressing Plasmodium infection. Studies on mosquito immunity revealed multiple factors that act as either facilitators or inhibitors of Plasmodium infection, but these findings were mostly based on single Anopheles-Plasmodium species combinations, not taking into account the diversity of mosquito and parasite species. We show that the functions of CTL4 and CTLMA2 have diverged in different vector species and can be both agonistic and antagonistic for Plasmodium infection. Their protection against parasite melanization in Anopheles gambiae is dependent on infection intensity, rather than the mosquito-parasite combination. Importantly, we describe for the first time how LRIM1 plays an essential role in Plasmodium infection of Anopheles albimanus, suggesting it is a key regulator of the poor vector competence of this species.
format	article
author	Maria L. Simões Godfree Mlambo Abhai Tripathi Yuemei Dong George Dimopoulos
author_facet	Maria L. Simões Godfree Mlambo Abhai Tripathi Yuemei Dong George Dimopoulos
author_sort	Maria L. Simões
title	Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
title_short	Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
title_full	Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
title_fullStr	Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
title_full_unstemmed	Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent
title_sort	immune regulation of <italic toggle="yes">plasmodium</italic> is <italic toggle="yes">anopheles</italic> species specific and infection intensity dependent
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/d90ef7a1a44b48d98090fa7f7968bec7
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Immune Regulation of <italic toggle="yes">Plasmodium</italic> Is <italic toggle="yes">Anopheles</italic> Species Specific and Infection Intensity Dependent

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