title: Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection.
abstract: Natural and experimental feline coronavirus (FCoV) infection leads to systemic viral spread via monocyte-associated viraemia and induces systemic proliferation of monocytes/macrophages. In the majority of naturally infected animals, FCoV infection remains subclinical and is associated with generalised B and T cell hyperplasia, but no other pathological findings. A minority of cats, however, develop feline infectious peritonitis (FIP), a fatal systemic granulomatous disease. This is generally accompanied by B and T cell depletion. The obvious functional differences of lymphatic tissues in FCoV-infected cats with and without FIP suggest that they contribute to the outcome of FCoV infection. This study attempted to evaluate the functional changes in haemolymphatic tissues after natural FCoV infection, with special emphasis on the magnitude, phenotype and function of the monocyte/macrophage population. The spleen, mesenteric lymph nodes and bone marrow from naturally FCoV-infected cats with and without FIP and specific pathogen-free (SPF) control cats were examined for the quantity and activation state of monocytes/macrophages both by immunohistology and by quantitative real time PCR for the transcription of interleukin (IL)-1beta, IL-6, IL-10, IL-12 p40, tumour necrosis factor (TNF), granulocyte colony stimulating factor (G-CSF), macrophage-CSF (M-CSF) and GM-CSF. Compared to cats with FIP, FCoV-infected cats without FIP exhibited significantly higher IL-10 levels in the spleen and significantly lower levels of IL-6, G- and M-CSF in mesenteric lymph nodes. In cats with FIP, however, IL-12 p40 levels were significantly lower in lymphatic tissues in comparison to both SPF cats and FCoV-infected cats without FIP. In comparison to SPF cats, FIP cats had significantly higher IL-1beta levels and lower TNF levels in mesenteric lymph nodes and lower M-CSF levels in the spleen. Findings indicate that FCoV-infected cats which do not develop FIP are able to mount an effective FCoV-specific immune response and can avoid excessive macrophage activation and FIP, possibly by upregulation of IL-10 production. Development of FIP, however, might be due to a lack of IL-12 which inhibits an effective cellular immune response and allows for monocyte/macrophage activation and the development of FIP.
authors.affiliation: Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Frankfurter Strasse 96, 35392 Giessen, Germany. akipar@liverpool.ac.uk
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Marina L
authors.initials: ML
authors.lastname: Meli
authors.forename: Klaus
authors.initials: K
authors.lastname: Failing
authors.forename: Tatjana
authors.initials: T
authors.lastname: Euler
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gomes-Keller
authors.forename: Dirk
authors.initials: D
authors.lastname: Schwartz
authors.forename: Hans
authors.initials: H
authors.lastname: Lutz
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinacher
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000821:virology; D002415:Cats; D016765:Coronavirus, Feline / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016766:Feline Infectious Peritonitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000821:virology; D014158:Transcription, Genetic
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D012333:RNA, Messenger