<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination

ABSTRACT The intracellular parasite Toxoplasma gondii infects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic...

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Autores principales:	Kirk D. C. Jensen, Ana Camejo, Mariane B. Melo, Cynthia Cordeiro, Lindsay Julien, Gijsbert M. Grotenbreg, Eva-Maria Frickel, Hidde L. Ploegh, Lucy Young, Jeroen P. J. Saeij
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/951858ac1fa54bed8b243d41124cc44a
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spelling	oai:doaj.org-article:951858ac1fa54bed8b243d41124cc44a2021-11-15T15:41:33Z<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination10.1128/mBio.02280-142150-7511https://doaj.org/article/951858ac1fa54bed8b243d41124cc44a2015-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02280-14https://doaj.org/toc/2150-7511ABSTRACT The intracellular parasite Toxoplasma gondii infects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic, multiple exposures to T. gondii likely occur with great frequency, yet little is known about the interaction between a chronically infected host and the parasite strains from these areas. A widely used model to explore secondary infection entails challenge of chronically infected or vaccinated mice with the highly virulent type I RH strain. Here, we show that although vaccinated or chronically infected C57BL/6 mice are protected against the type I RH strain, they are not protected against challenge with most strains prevalent in South America or another type I strain, GT1. Genetic and genomic analyses implicated the parasite-secreted rhoptry effectors ROP5 and ROP18, which antagonize the host's gamma interferon-induced immunity-regulated GTPases (IRGs), as primary requirements for virulence during secondary infection. ROP5 and ROP18 promoted parasite superinfection in the brains of challenged survivors. We hypothesize that superinfection may be an important mechanism to generate T. gondii strain diversity, simply because two parasite strains would be present in a single meal consumed by the feline definitive host. Superinfection may drive the genetic diversity of Toxoplasma strains in South America, where most isolates are IRG resistant, compared to North America, where most strains are IRG susceptible and are derived from a few clonal lineages. In summary, ROP5 and ROP18 promote Toxoplasma virulence during reinfection. IMPORTANCE Toxoplasma gondii is a widespread parasite of warm-blooded animals and currently infects one-third of the human population. A long-standing assumption in the field is that prior exposure to this parasite protects the host from subsequent reexposure, due to the generation of protective immunological memory. However, this assumption is based on clinical data and mouse models that analyze infections with strains common to Europe infections with strains common to Europe and North America. In contrast, we found that the majority of strains sampled from around the world, in particular those from South America, were able to kill or reinfect the brains of hosts previously exposed to T. gondii. The T. gondii virulence factors ROP5 and ROP18, which inhibit key host effectors that mediate parasite killing, were required for these phenotypes. We speculate that these results underpin clinical observations that pregnant women previously exposed to Toxoplasma can develop congenital infection upon reexposure to South American strains.Kirk D. C. JensenAna CamejoMariane B. MeloCynthia CordeiroLindsay JulienGijsbert M. GrotenbregEva-Maria FrickelHidde L. PloeghLucy YoungJeroen P. J. SaeijAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 2 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kirk D. C. Jensen Ana Camejo Mariane B. Melo Cynthia Cordeiro Lindsay Julien Gijsbert M. Grotenbreg Eva-Maria Frickel Hidde L. Ploegh Lucy Young Jeroen P. J. Saeij <named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
description	ABSTRACT The intracellular parasite Toxoplasma gondii infects a wide variety of vertebrate species globally. Infection in most hosts causes a lifelong chronic infection and generates immunological memory responses that protect the host against new infections. In regions where the organism is endemic, multiple exposures to T. gondii likely occur with great frequency, yet little is known about the interaction between a chronically infected host and the parasite strains from these areas. A widely used model to explore secondary infection entails challenge of chronically infected or vaccinated mice with the highly virulent type I RH strain. Here, we show that although vaccinated or chronically infected C57BL/6 mice are protected against the type I RH strain, they are not protected against challenge with most strains prevalent in South America or another type I strain, GT1. Genetic and genomic analyses implicated the parasite-secreted rhoptry effectors ROP5 and ROP18, which antagonize the host's gamma interferon-induced immunity-regulated GTPases (IRGs), as primary requirements for virulence during secondary infection. ROP5 and ROP18 promoted parasite superinfection in the brains of challenged survivors. We hypothesize that superinfection may be an important mechanism to generate T. gondii strain diversity, simply because two parasite strains would be present in a single meal consumed by the feline definitive host. Superinfection may drive the genetic diversity of Toxoplasma strains in South America, where most isolates are IRG resistant, compared to North America, where most strains are IRG susceptible and are derived from a few clonal lineages. In summary, ROP5 and ROP18 promote Toxoplasma virulence during reinfection. IMPORTANCE Toxoplasma gondii is a widespread parasite of warm-blooded animals and currently infects one-third of the human population. A long-standing assumption in the field is that prior exposure to this parasite protects the host from subsequent reexposure, due to the generation of protective immunological memory. However, this assumption is based on clinical data and mouse models that analyze infections with strains common to Europe infections with strains common to Europe and North America. In contrast, we found that the majority of strains sampled from around the world, in particular those from South America, were able to kill or reinfect the brains of hosts previously exposed to T. gondii. The T. gondii virulence factors ROP5 and ROP18, which inhibit key host effectors that mediate parasite killing, were required for these phenotypes. We speculate that these results underpin clinical observations that pregnant women previously exposed to Toxoplasma can develop congenital infection upon reexposure to South American strains.
format	article
author	Kirk D. C. Jensen Ana Camejo Mariane B. Melo Cynthia Cordeiro Lindsay Julien Gijsbert M. Grotenbreg Eva-Maria Frickel Hidde L. Ploegh Lucy Young Jeroen P. J. Saeij
author_facet	Kirk D. C. Jensen Ana Camejo Mariane B. Melo Cynthia Cordeiro Lindsay Julien Gijsbert M. Grotenbreg Eva-Maria Frickel Hidde L. Ploegh Lucy Young Jeroen P. J. Saeij
author_sort	Kirk D. C. Jensen
title	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
title_short	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
title_full	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
title_fullStr	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
title_full_unstemmed	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination
title_sort	<named-content content-type="genus-species">toxoplasma gondii</named-content> superinfection and virulence during secondary infection correlate with the exact <italic toggle="yes">rop5/rop18</italic> allelic combination
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/951858ac1fa54bed8b243d41124cc44a
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<named-content content-type="genus-species">Toxoplasma gondii</named-content> Superinfection and Virulence during Secondary Infection Correlate with the Exact <italic toggle="yes">ROP5/ROP18</italic> Allelic Combination

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