The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model

ABSTRACT Cryptococcosis is caused by the opportunistic pathogen Cryptococcus neoformans or by the primary pathogen Cryptococcus gattii. Epidemiological studies suggest that patients infected with C. gattii mainly present with pulmonary disease, while those infected with C. neoformans commonly manife...

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Autores principales:	Popchai Ngamskulrungroj, Yun Chang, Edward Sionov, Kyung J. Kwon-Chung
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/49526e03951d4aefa011ca8b7b18db6c
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spelling	oai:doaj.org-article:49526e03951d4aefa011ca8b7b18db6c2021-11-15T15:39:02ZThe Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model10.1128/mBio.00103-122150-7511https://doaj.org/article/49526e03951d4aefa011ca8b7b18db6c2012-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00103-12https://doaj.org/toc/2150-7511ABSTRACT Cryptococcosis is caused by the opportunistic pathogen Cryptococcus neoformans or by the primary pathogen Cryptococcus gattii. Epidemiological studies suggest that patients infected with C. gattii mainly present with pulmonary disease, while those infected with C. neoformans commonly manifest meningoencephalitis. We compared the pathogenesis of the two species using the C. neoformans H99 and C. gattii R265 strains in a murine inhalation model. C. neoformans grew faster in the brain and caused death by meningoencephalitis, while C. gattii grew faster in the lungs and caused death without producing fulminating meningoencephalitis. Despite the consistent failure to recover R265 cells from blood, a fraction of the R265 population was detected in the extrapulmonary organs, including the brain. Upon intravenous (i.v. ) inoculation of 104 cells via the tail vein, however, C. gattii produced severe meningoencephalitis, demonstrating that C. gattii cells can efficiently cross the blood-brain barrier. Interestingly, i.v. inoculation with five cells caused brain infection in only 10% of C. gattii-infected mice, compared to 60% of mice infected with C. neoformans. In mice that had been initially inoculated via the pulmonary route and subsequently challenged intravenously, a protective effect was observed only in mice infected with C. gattii. C. neoformans cells grew 10 to 100 times faster than C. gattii cells in blood or serum collected from naive mice. The paucity of meningoencephalitis upon inhalation of C. gattii, therefore, may be partly due to an unknown factor(s) in the host’s blood coupled with immune protection that reduces dissemination to the brain and fosters lung infection. IMPORTANCE While Cryptococcus neoformans is the most common cause of fatal meningoencephalitis, especially in HIV patients, Cryptococcus gattii causes disease mainly in non-HIV patients. Clinical studies revealed that most patients infected with C. gattii VGII strains have lung infections with minimal brain involvement. Despite extensive clinicopathological studies on cryptococcosis in animal models, only a few have included C. gattii. We compared the pathogenesis of the two species in mice using an inhalation model. Similar to infection in humans, even though C. gattii can cross the blood-brain barrier, it failed to cause fatal meningoencephalitis but caused fatal lung infection. We show that growth of C. gattii in mouse blood is significantly slower than that of C. neoformans and that a secondary protective phenomenon, though weak, manifests itself only in C. gattii infection. Our study provides a model for understanding the clinicopathological differences between these two closely genetically related pathogens.Popchai NgamskulrungrojYun ChangEdward SionovKyung J. Kwon-ChungAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 3 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Popchai Ngamskulrungroj Yun Chang Edward Sionov Kyung J. Kwon-Chung The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
description	ABSTRACT Cryptococcosis is caused by the opportunistic pathogen Cryptococcus neoformans or by the primary pathogen Cryptococcus gattii. Epidemiological studies suggest that patients infected with C. gattii mainly present with pulmonary disease, while those infected with C. neoformans commonly manifest meningoencephalitis. We compared the pathogenesis of the two species using the C. neoformans H99 and C. gattii R265 strains in a murine inhalation model. C. neoformans grew faster in the brain and caused death by meningoencephalitis, while C. gattii grew faster in the lungs and caused death without producing fulminating meningoencephalitis. Despite the consistent failure to recover R265 cells from blood, a fraction of the R265 population was detected in the extrapulmonary organs, including the brain. Upon intravenous (i.v. ) inoculation of 104 cells via the tail vein, however, C. gattii produced severe meningoencephalitis, demonstrating that C. gattii cells can efficiently cross the blood-brain barrier. Interestingly, i.v. inoculation with five cells caused brain infection in only 10% of C. gattii-infected mice, compared to 60% of mice infected with C. neoformans. In mice that had been initially inoculated via the pulmonary route and subsequently challenged intravenously, a protective effect was observed only in mice infected with C. gattii. C. neoformans cells grew 10 to 100 times faster than C. gattii cells in blood or serum collected from naive mice. The paucity of meningoencephalitis upon inhalation of C. gattii, therefore, may be partly due to an unknown factor(s) in the host’s blood coupled with immune protection that reduces dissemination to the brain and fosters lung infection. IMPORTANCE While Cryptococcus neoformans is the most common cause of fatal meningoencephalitis, especially in HIV patients, Cryptococcus gattii causes disease mainly in non-HIV patients. Clinical studies revealed that most patients infected with C. gattii VGII strains have lung infections with minimal brain involvement. Despite extensive clinicopathological studies on cryptococcosis in animal models, only a few have included C. gattii. We compared the pathogenesis of the two species in mice using an inhalation model. Similar to infection in humans, even though C. gattii can cross the blood-brain barrier, it failed to cause fatal meningoencephalitis but caused fatal lung infection. We show that growth of C. gattii in mouse blood is significantly slower than that of C. neoformans and that a secondary protective phenomenon, though weak, manifests itself only in C. gattii infection. Our study provides a model for understanding the clinicopathological differences between these two closely genetically related pathogens.
format	article
author	Popchai Ngamskulrungroj Yun Chang Edward Sionov Kyung J. Kwon-Chung
author_facet	Popchai Ngamskulrungroj Yun Chang Edward Sionov Kyung J. Kwon-Chung
author_sort	Popchai Ngamskulrungroj
title	The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
title_short	The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
title_full	The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
title_fullStr	The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
title_full_unstemmed	The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model
title_sort	primary target organ of <named-content content-type="genus-species">cryptococcus gattii</named-content> is different from that of <named-content content-type="genus-species">cryptococcus neoformans</named-content> in a murine model
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/49526e03951d4aefa011ca8b7b18db6c
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The Primary Target Organ of <named-content content-type="genus-species">Cryptococcus gattii</named-content> Is Different from That of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in a Murine Model

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