Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination

ABSTRACT Cryptococcus neoformans is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dis...

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Autores principales:	Carolina Coelho, Emma Camacho, Antonio Salas, Alexandre Alanio, Arturo Casadevall
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Cryptococcus Cryptococcus gattii Cryptococcus neoformans brain infection nose Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/de5786871ae34a73b839d8c0c3657025
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spelling	oai:doaj.org-article:de5786871ae34a73b839d8c0c36570252021-11-15T15:22:26ZIntranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination10.1128/mSphere.00483-192379-5042https://doaj.org/article/de5786871ae34a73b839d8c0c36570252019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00483-19https://doaj.org/toc/2379-5042ABSTRACT Cryptococcus neoformans is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via either transport by free yeast cells in the bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal models. All three modes of infection resulted in dissemination of C. neoformans to the brain in less than 3 h. Further, C. neoformans was detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery, but our findings show that instillation of C. neoformans produces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume that the initial sites of infection of infection are brain, lung, and upper respiratory tract, including the nasal airways. IMPORTANCE Cryptococcus neoformans causes an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS. C. neoformans has a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources, after which the fungus lays dormant within the human body. Upon AIDS-induced immunosuppression or therapy-induced immunosuppression (required for organ transplant recipients or those suffering from autoimmune disorders), cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study showed that upon contact with the host, C. neoformans can quickly (a few hours) reach the host brain and also colonizes the nose of infected animals. Therefore, this work paves the way to better knowledge of how C. neoformans travels through the host body. Understanding how C. neoformans infects, disseminates, and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.Carolina CoelhoEmma CamachoAntonio SalasAlexandre AlanioArturo CasadevallAmerican Society for MicrobiologyarticleCryptococcusCryptococcus gattiiCryptococcus neoformansbraininfectionnoseMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryptococcus Cryptococcus gattii Cryptococcus neoformans brain infection nose Microbiology QR1-502
spellingShingle	Cryptococcus Cryptococcus gattii Cryptococcus neoformans brain infection nose Microbiology QR1-502 Carolina Coelho Emma Camacho Antonio Salas Alexandre Alanio Arturo Casadevall Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
description	ABSTRACT Cryptococcus neoformans is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via either transport by free yeast cells in the bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal models. All three modes of infection resulted in dissemination of C. neoformans to the brain in less than 3 h. Further, C. neoformans was detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery, but our findings show that instillation of C. neoformans produces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume that the initial sites of infection of infection are brain, lung, and upper respiratory tract, including the nasal airways. IMPORTANCE Cryptococcus neoformans causes an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS. C. neoformans has a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources, after which the fungus lays dormant within the human body. Upon AIDS-induced immunosuppression or therapy-induced immunosuppression (required for organ transplant recipients or those suffering from autoimmune disorders), cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study showed that upon contact with the host, C. neoformans can quickly (a few hours) reach the host brain and also colonizes the nose of infected animals. Therefore, this work paves the way to better knowledge of how C. neoformans travels through the host body. Understanding how C. neoformans infects, disseminates, and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.
format	article
author	Carolina Coelho Emma Camacho Antonio Salas Alexandre Alanio Arturo Casadevall
author_facet	Carolina Coelho Emma Camacho Antonio Salas Alexandre Alanio Arturo Casadevall
author_sort	Carolina Coelho
title	Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
title_short	Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
title_full	Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
title_fullStr	Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
title_full_unstemmed	Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination
title_sort	intranasal inoculation of <named-content content-type="genus-species">cryptococcus neoformans</named-content> in mice produces nasal infection with rapid brain dissemination
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/de5786871ae34a73b839d8c0c3657025
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Intranasal Inoculation of <named-content content-type="genus-species">Cryptococcus neoformans</named-content> in Mice Produces Nasal Infection with Rapid Brain Dissemination

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