Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice
The complement system (CS) contributes to the initial containment of viral and bacterial pathogens and clearance of dying cells in circulation. We previously reported mice deficient in complement component 3 (C3KO mice) were more sensitive than wild-type (WT) mice to ocular HSV-1 infection, as measu...
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MDPI AG
2024-01-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/13/1/74 |
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| author | Daniel J. J. Carr Adrian Filiberti Grzegorz B. Gmyrek |
| author_facet | Daniel J. J. Carr Adrian Filiberti Grzegorz B. Gmyrek |
| author_sort | Daniel J. J. Carr |
| collection | DOAJ |
| description | The complement system (CS) contributes to the initial containment of viral and bacterial pathogens and clearance of dying cells in circulation. We previously reported mice deficient in complement component 3 (C3KO mice) were more sensitive than wild-type (WT) mice to ocular HSV-1 infection, as measured by a reduction in cumulative survival and elevated viral titers in the nervous system but not the cornea between days three and seven post infection (pi). The present study was undertaken to determine if complement deficiency impacted virus replication and associated changes in inflammation at earlier time points in the cornea. C3KO mice were found to possess significantly (<i>p</i> < 0.05) less infectious virus in the cornea at 24 h pi that corresponded with a decrease in HSV-1 lytic gene expression at 12 and 24 h pi compared to WT animals. Flow cytometry acquisition found no differences in the myeloid cell populations residing in the cornea including total macrophage and neutrophil populations at 24 h pi with minimal infiltrating cell populations detected at the 12 h pi time point. Analysis of cytokine and chemokine content in the cornea measured at 12 and 24 h pi revealed that only CCL3 (MIP-1α) was found to be different between WT and C3KO mice with >2-fold increased levels (<i>p</i> < 0.05, ANOVA and Tukey’s post hoc <i>t</i>-test) in the cornea of WT mice at 12 h pi. C3KO mouse resistance to HSV-1 infection at the early time points correlated with a significant increase in type I interferon (IFN) gene expression including IFN-α1 and IFN-β and downstream effector genes including tetherin and RNase L (<i>p</i> < 0.05, Mann–Whitney rank order test). These results suggest early activation of the CS interferes with the induction of the type I IFN response and leads to a transient increase in virus replication following corneal HSV-1 infection. |
| first_indexed | 2024-03-08T10:38:04Z |
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| language | English |
| last_indexed | 2024-03-08T10:38:04Z |
| publishDate | 2024-01-01 |
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| series | Pathogens |
| spelling | doaj.art-150aead7fe4a47b3adec06bbb3b0b8002024-01-26T18:03:48ZengMDPI AGPathogens2076-08172024-01-011317410.3390/pathogens13010074Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in MiceDaniel J. J. Carr0Adrian Filiberti1Grzegorz B. Gmyrek2Department of Ophthalmology, Microbiology, and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe complement system (CS) contributes to the initial containment of viral and bacterial pathogens and clearance of dying cells in circulation. We previously reported mice deficient in complement component 3 (C3KO mice) were more sensitive than wild-type (WT) mice to ocular HSV-1 infection, as measured by a reduction in cumulative survival and elevated viral titers in the nervous system but not the cornea between days three and seven post infection (pi). The present study was undertaken to determine if complement deficiency impacted virus replication and associated changes in inflammation at earlier time points in the cornea. C3KO mice were found to possess significantly (<i>p</i> < 0.05) less infectious virus in the cornea at 24 h pi that corresponded with a decrease in HSV-1 lytic gene expression at 12 and 24 h pi compared to WT animals. Flow cytometry acquisition found no differences in the myeloid cell populations residing in the cornea including total macrophage and neutrophil populations at 24 h pi with minimal infiltrating cell populations detected at the 12 h pi time point. Analysis of cytokine and chemokine content in the cornea measured at 12 and 24 h pi revealed that only CCL3 (MIP-1α) was found to be different between WT and C3KO mice with >2-fold increased levels (<i>p</i> < 0.05, ANOVA and Tukey’s post hoc <i>t</i>-test) in the cornea of WT mice at 12 h pi. C3KO mouse resistance to HSV-1 infection at the early time points correlated with a significant increase in type I interferon (IFN) gene expression including IFN-α1 and IFN-β and downstream effector genes including tetherin and RNase L (<i>p</i> < 0.05, Mann–Whitney rank order test). These results suggest early activation of the CS interferes with the induction of the type I IFN response and leads to a transient increase in virus replication following corneal HSV-1 infection.https://www.mdpi.com/2076-0817/13/1/74complementherpes simplex virus type 1corneacytokineschemokinesinterferon |
| spellingShingle | Daniel J. J. Carr Adrian Filiberti Grzegorz B. Gmyrek Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice Pathogens complement herpes simplex virus type 1 cornea cytokines chemokines interferon |
| title | Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice |
| title_full | Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice |
| title_fullStr | Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice |
| title_full_unstemmed | Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice |
| title_short | Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice |
| title_sort | complement suppresses the initial type 1 interferon response to ocular herpes simplex virus type 1 infection in mice |
| topic | complement herpes simplex virus type 1 cornea cytokines chemokines interferon |
| url | https://www.mdpi.com/2076-0817/13/1/74 |
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