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Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis
PURPOSE: To explore the consequences of innate interference on intraocular inflammatory responses during Bacillus endophthalmitis. METHODS: Bacillus endophthalmitis was induced in mice. Innate immune pathway activation was interfered by injecting S layer protein-deficient (∆slpA) B. thuringiensis or...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671874/ https://www.ncbi.nlm.nih.gov/pubmed/33180117 http://dx.doi.org/10.1167/iovs.61.13.17 |
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author | Mursalin, Md Huzzatul Coburn, Phillip S. Miller, Frederick C. Livingston, Erin T. Astley, Roger Callegan, Michelle C. |
author_facet | Mursalin, Md Huzzatul Coburn, Phillip S. Miller, Frederick C. Livingston, Erin T. Astley, Roger Callegan, Michelle C. |
author_sort | Mursalin, Md Huzzatul |
collection | PubMed |
description | PURPOSE: To explore the consequences of innate interference on intraocular inflammatory responses during Bacillus endophthalmitis. METHODS: Bacillus endophthalmitis was induced in mice. Innate immune pathway activation was interfered by injecting S layer protein-deficient (∆slpA) B. thuringiensis or by treating wild-type (WT)–infected mice with a TLR2/4 inhibitor (WT+OxPAPC). At 10 hours postinfection, eyes were harvested and RNA was purified. A NanoString murine inflammation panel was used to compare gene expression in WT-infected, WT+OxPAPC, ∆slpA-infected, and uninfected eyes. RESULTS: In WT-infected eyes, 56% of genes were significantly upregulated compared to uninfected controls. Compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and ∆slpA-infected eyes, respectively. Expression of 61 genes that were upregulated in WT-infected eyes was decreased in WT+OxPAPC and ∆slpA-infected eyes. Innate interference resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate pathway genes (TLRs 2, 4, 6, and 8, MyD88, Nod2, Nlrp3, NF-κB, STAT3, RelA, RelB, and Ptgs2). Innate interference also reduced the expression of several inflammatory cytokines (CSF2, CSF3, IL-6, IL-1β, IL-1α, TNFα, IL-23α, TGFβ1, and IL-12β) and chemokines (CCL2, CCL3, and CXCLs 1, 2, 3, 5, 9, and 10). All of the aforementioned genes were significantly upregulated in WT-infected eyes. CONCLUSIONS: These results suggest that interfering with innate activation significantly reduced the intraocular inflammatory response in Bacillus endophthalmitis. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment. |
format | Online Article Text |
id | pubmed-7671874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-76718742020-11-20 Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis Mursalin, Md Huzzatul Coburn, Phillip S. Miller, Frederick C. Livingston, Erin T. Astley, Roger Callegan, Michelle C. Invest Ophthalmol Vis Sci Immunology and Microbiology PURPOSE: To explore the consequences of innate interference on intraocular inflammatory responses during Bacillus endophthalmitis. METHODS: Bacillus endophthalmitis was induced in mice. Innate immune pathway activation was interfered by injecting S layer protein-deficient (∆slpA) B. thuringiensis or by treating wild-type (WT)–infected mice with a TLR2/4 inhibitor (WT+OxPAPC). At 10 hours postinfection, eyes were harvested and RNA was purified. A NanoString murine inflammation panel was used to compare gene expression in WT-infected, WT+OxPAPC, ∆slpA-infected, and uninfected eyes. RESULTS: In WT-infected eyes, 56% of genes were significantly upregulated compared to uninfected controls. Compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and ∆slpA-infected eyes, respectively. Expression of 61 genes that were upregulated in WT-infected eyes was decreased in WT+OxPAPC and ∆slpA-infected eyes. Innate interference resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate pathway genes (TLRs 2, 4, 6, and 8, MyD88, Nod2, Nlrp3, NF-κB, STAT3, RelA, RelB, and Ptgs2). Innate interference also reduced the expression of several inflammatory cytokines (CSF2, CSF3, IL-6, IL-1β, IL-1α, TNFα, IL-23α, TGFβ1, and IL-12β) and chemokines (CCL2, CCL3, and CXCLs 1, 2, 3, 5, 9, and 10). All of the aforementioned genes were significantly upregulated in WT-infected eyes. CONCLUSIONS: These results suggest that interfering with innate activation significantly reduced the intraocular inflammatory response in Bacillus endophthalmitis. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment. The Association for Research in Vision and Ophthalmology 2020-11-12 /pmc/articles/PMC7671874/ /pubmed/33180117 http://dx.doi.org/10.1167/iovs.61.13.17 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Immunology and Microbiology Mursalin, Md Huzzatul Coburn, Phillip S. Miller, Frederick C. Livingston, Erin T. Astley, Roger Callegan, Michelle C. Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title | Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title_full | Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title_fullStr | Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title_full_unstemmed | Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title_short | Innate Immune Interference Attenuates Inflammation In Bacillus Endophthalmitis |
title_sort | innate immune interference attenuates inflammation in bacillus endophthalmitis |
topic | Immunology and Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671874/ https://www.ncbi.nlm.nih.gov/pubmed/33180117 http://dx.doi.org/10.1167/iovs.61.13.17 |
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