Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice
Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We rep...
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| Format: | Article |
| Language: | English |
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2016
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| Online Access: | http://eprints.uanl.mx/14792/1/26.pdf |
| _version_ | 1838550986245799936 |
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| author | Larcombe, Alexander Mifuji Lira, Roque Masaharu Limón Flores, Alberto Yairh Salinas Carmona, Mario César Ortiz Stern, Alejandro |
| author_facet | Larcombe, Alexander Mifuji Lira, Roque Masaharu Limón Flores, Alberto Yairh Salinas Carmona, Mario César Ortiz Stern, Alejandro |
| author_sort | Larcombe, Alexander |
| collection | Repositorio Institucional |
| description | Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the
lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection.
Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial
doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of
nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice. |
| format | Article |
| id | eprints-14792 |
| institution | UANL |
| language | English |
| publishDate | 2016 |
| record_format | eprints |
| spelling | eprints-147922025-07-16T16:00:15Z http://eprints.uanl.mx/14792/ Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice Larcombe, Alexander Mifuji Lira, Roque Masaharu Limón Flores, Alberto Yairh Salinas Carmona, Mario César Ortiz Stern, Alejandro RC Medicina Interna, Psiquiatría, Neurología Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice. 2016 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/14792/1/26.pdf http://eprints.uanl.mx/14792/1.haspreviewThumbnailVersion/26.pdf Larcombe, Alexander y Mifuji Lira, Roque Masaharu y Limón Flores, Alberto Yairh y Salinas Carmona, Mario César y Ortiz Stern, Alejandro (2016) Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice. PLOS ONE, 11 (6). pp. 1-16. ISSN 1932-6203 http://doi.org/10.1371/journal.pone.0157475 doi:10.1371/journal.pone.0157475 |
| spellingShingle | RC Medicina Interna, Psiquiatría, Neurología Larcombe, Alexander Mifuji Lira, Roque Masaharu Limón Flores, Alberto Yairh Salinas Carmona, Mario César Ortiz Stern, Alejandro Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| title_full | Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| title_fullStr | Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| title_full_unstemmed | Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| title_short | Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice |
| title_sort | experimental granulomatous pulmonary nocardiosis in balb c mice |
| topic | RC Medicina Interna, Psiquiatría, Neurología |
| url | http://eprints.uanl.mx/14792/1/26.pdf |
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