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Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice
Despite Aspergillus being the leading cause of exogenous fungal endophthalmitis following traumatic injury to the eye, its pathogenesis is not fully understood. In the current study, we developed a murine model of Aspergillus fumigatus (AF) endophthalmitis and investigated the disease pathobiology....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780922/ https://www.ncbi.nlm.nih.gov/pubmed/31466325 http://dx.doi.org/10.3390/microorganisms7090297 |
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author | Gupta, Neha Singh, Pawan Kumar Revankar, Sanjay G. Chandrasekar, Pranatharthi H. Kumar, Ashok |
author_facet | Gupta, Neha Singh, Pawan Kumar Revankar, Sanjay G. Chandrasekar, Pranatharthi H. Kumar, Ashok |
author_sort | Gupta, Neha |
collection | PubMed |
description | Despite Aspergillus being the leading cause of exogenous fungal endophthalmitis following traumatic injury to the eye, its pathogenesis is not fully understood. In the current study, we developed a murine model of Aspergillus fumigatus (AF) endophthalmitis and investigated the disease pathobiology. Endophthalmitis was induced by intravitreal injection of Aspergillus spores in immunocompetent and immunocompromised (neutropenic) C57BL/6 mice, and disease severity was assessed by eye exam, fungal burden estimation, and histological examination. Our data showed that AF infection caused a time-dependent increase in corneal haze, opacity, and hypopyon beginning at two days post-infection (DPI). The fungal burden in infected eyes of immunocompetent mice peaked at 2 DPI and declined over 9 DPI. AF-infected neuroretina exhibited induction of innate immune response via upregulation of Toll-like receptors (TLRs) and inflammatory mediators (TNFα, IL-1β, and IL6), and increased polymorphonuclear neutrophil (PMN) infiltration. Histological analysis revealed heavy cellular infiltrates in the vitreous cavity as well as disruption of normal retinal architecture and increased retinal cell death. Neutropenic mice exhibited severe disease pathology with the prolonged fungal burden and increased inflammatory mediators. Our study described the first immunocompetent murine model of exogenous AF endophthalmitis and demonstrated an important role of neutrophils in innate defense against fungal endophthalmitis. |
format | Online Article Text |
id | pubmed-6780922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67809222019-10-30 Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice Gupta, Neha Singh, Pawan Kumar Revankar, Sanjay G. Chandrasekar, Pranatharthi H. Kumar, Ashok Microorganisms Article Despite Aspergillus being the leading cause of exogenous fungal endophthalmitis following traumatic injury to the eye, its pathogenesis is not fully understood. In the current study, we developed a murine model of Aspergillus fumigatus (AF) endophthalmitis and investigated the disease pathobiology. Endophthalmitis was induced by intravitreal injection of Aspergillus spores in immunocompetent and immunocompromised (neutropenic) C57BL/6 mice, and disease severity was assessed by eye exam, fungal burden estimation, and histological examination. Our data showed that AF infection caused a time-dependent increase in corneal haze, opacity, and hypopyon beginning at two days post-infection (DPI). The fungal burden in infected eyes of immunocompetent mice peaked at 2 DPI and declined over 9 DPI. AF-infected neuroretina exhibited induction of innate immune response via upregulation of Toll-like receptors (TLRs) and inflammatory mediators (TNFα, IL-1β, and IL6), and increased polymorphonuclear neutrophil (PMN) infiltration. Histological analysis revealed heavy cellular infiltrates in the vitreous cavity as well as disruption of normal retinal architecture and increased retinal cell death. Neutropenic mice exhibited severe disease pathology with the prolonged fungal burden and increased inflammatory mediators. Our study described the first immunocompetent murine model of exogenous AF endophthalmitis and demonstrated an important role of neutrophils in innate defense against fungal endophthalmitis. MDPI 2019-08-28 /pmc/articles/PMC6780922/ /pubmed/31466325 http://dx.doi.org/10.3390/microorganisms7090297 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gupta, Neha Singh, Pawan Kumar Revankar, Sanjay G. Chandrasekar, Pranatharthi H. Kumar, Ashok Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title | Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title_full | Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title_fullStr | Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title_full_unstemmed | Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title_short | Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice |
title_sort | pathobiology of aspergillus fumigatus endophthalmitis in immunocompetent and immunocompromised mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780922/ https://www.ncbi.nlm.nih.gov/pubmed/31466325 http://dx.doi.org/10.3390/microorganisms7090297 |
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