Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach
Feline coronavirus (FCoV) infection initiates monocyte-associated viremia and viral persistence. Virus-infected, -activated monocytes also trigger feline infectious peritonitis (FIP), a fatal systemic disease of felids typified by granulomatous (peri)phlebitis. Currently, the exact mechanisms induci...
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MDPI AG
2020-10-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/11/893 |
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| author | Alexandra J. Malbon Eleni Michalopoulou Marina L. Meli Emi N. Barker Séverine Tasker Keith Baptiste Anja Kipar |
| author_facet | Alexandra J. Malbon Eleni Michalopoulou Marina L. Meli Emi N. Barker Séverine Tasker Keith Baptiste Anja Kipar |
| author_sort | Alexandra J. Malbon |
| collection | DOAJ |
| description | Feline coronavirus (FCoV) infection initiates monocyte-associated viremia and viral persistence. Virus-infected, -activated monocytes also trigger feline infectious peritonitis (FIP), a fatal systemic disease of felids typified by granulomatous (peri)phlebitis. Currently, the exact mechanisms inducing monocyte activation and FIP are unknown. This study attempted to identify the potential immediate effect of virulent FCoV on colony-stimulating factor (CSF) (granulocyte (G)-CSF, monocyte (M)-CSF and granulocyte-monocyte (GM)-CSF levels through in vitro assessment, alongside prototypical pro- and anti-inflammatory mediators (interleukin (IL)-1, IL-6, IL-12p40, tumor necrosis factor (TNF)-α, and IL-10); this was assessed alongside the in vivo situation in the hemolymphatic tissues of cats euthanized with natural end-stage FIP. For the in vitro work, isolated monocytes from SPF cats were cultured short-term and infected with the FIP virus (FIPV) strain DF2. Mediator transcription was assessed by quantitative reverse transcriptase PCR (RT-qPCR) at 3, 6 and 9 h post infection (hpi), and in the post-mortem samples of bone marrow, spleen, and mesenteric lymph nodes (MLN) of cats with FIP. We observed limited and transient changes in cytokine transcription in monocytes after infection, i.e., a significant increase of IL-6 at 3 hpi and of GM-CSF over the 3 and 6 hpi period, whereas M-CSF was significantly decreased at 9 hpi, with a limited effect of age. The findings indicate that the infection induces expansion of the monocyte/macrophage population, which would ensure the sufficient supply of cells for consistent viral replication. In natural disease, the only upregulation was of G-CSF in the MLN, suggesting either immune exhaustion or an active downregulation by the host as part of its viral response. |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T15:17:42Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-485dcf6a6a494a77bd1b8bcecd08cafc2023-11-20T18:45:50ZengMDPI AGPathogens2076-08172020-10-0191189310.3390/pathogens9110893Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro ApproachAlexandra J. Malbon0Eleni Michalopoulou1Marina L. Meli2Emi N. Barker3Séverine Tasker4Keith Baptiste5Anja Kipar6Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, SwitzerlandDepartment of Livestock and One Health, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Neston CH64 7TE, UKCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, SwitzerlandBristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKBristol Veterinary School, University of Bristol, Langford, Bristol BS40 5DU, UKDepartment of Veterinary Medicine, Danish Medicines Agency (Lægemiddelstryelsen), Axel Heides gade 1, DK-2300 Copenhagen South, DenmarkInstitute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, SwitzerlandFeline coronavirus (FCoV) infection initiates monocyte-associated viremia and viral persistence. Virus-infected, -activated monocytes also trigger feline infectious peritonitis (FIP), a fatal systemic disease of felids typified by granulomatous (peri)phlebitis. Currently, the exact mechanisms inducing monocyte activation and FIP are unknown. This study attempted to identify the potential immediate effect of virulent FCoV on colony-stimulating factor (CSF) (granulocyte (G)-CSF, monocyte (M)-CSF and granulocyte-monocyte (GM)-CSF levels through in vitro assessment, alongside prototypical pro- and anti-inflammatory mediators (interleukin (IL)-1, IL-6, IL-12p40, tumor necrosis factor (TNF)-α, and IL-10); this was assessed alongside the in vivo situation in the hemolymphatic tissues of cats euthanized with natural end-stage FIP. For the in vitro work, isolated monocytes from SPF cats were cultured short-term and infected with the FIP virus (FIPV) strain DF2. Mediator transcription was assessed by quantitative reverse transcriptase PCR (RT-qPCR) at 3, 6 and 9 h post infection (hpi), and in the post-mortem samples of bone marrow, spleen, and mesenteric lymph nodes (MLN) of cats with FIP. We observed limited and transient changes in cytokine transcription in monocytes after infection, i.e., a significant increase of IL-6 at 3 hpi and of GM-CSF over the 3 and 6 hpi period, whereas M-CSF was significantly decreased at 9 hpi, with a limited effect of age. The findings indicate that the infection induces expansion of the monocyte/macrophage population, which would ensure the sufficient supply of cells for consistent viral replication. In natural disease, the only upregulation was of G-CSF in the MLN, suggesting either immune exhaustion or an active downregulation by the host as part of its viral response.https://www.mdpi.com/2076-0817/9/11/893feline coronavirusfeline infectious peritonitismonocyte proliferationcolony stimulating factors |
| spellingShingle | Alexandra J. Malbon Eleni Michalopoulou Marina L. Meli Emi N. Barker Séverine Tasker Keith Baptiste Anja Kipar Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach Pathogens feline coronavirus feline infectious peritonitis monocyte proliferation colony stimulating factors |
| title | Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach |
| title_full | Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach |
| title_fullStr | Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach |
| title_full_unstemmed | Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach |
| title_short | Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach |
| title_sort | colony stimulating factors in early feline infectious peritonitis virus infection of monocytes and in end stage feline infectious peritonitis a combined in vivo and in vitro approach |
| topic | feline coronavirus feline infectious peritonitis monocyte proliferation colony stimulating factors |
| url | https://www.mdpi.com/2076-0817/9/11/893 |
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