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. 2006 Aug 15;112(3-4):141-55.
doi: 10.1016/j.vetimm.2006.02.004. Epub 2006 Apr 18.

Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection

Anja Kipar  1 , Marina L Meli, Klaus Failing, Tatjana Euler, Maria A Gomes-Keller, Dirk Schwartz, Hans Lutz, Manfred Reinacher
Affiliations

Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection

Anja Kipar et al. Vet Immunol Immunopathol. .

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.

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Figures

Fig. 1
Fig. 1
Comparison of macrophage populations in SPF cats (n = 14), cats with FIP (n = 15) and FCoV-infected cats without FIP (n = 13). (a) Percentage of myeloid/histiocyte antigen-positive cells among cells in the splenic red pulp. (b) Percentage of CD18-positive cells among cells in the splenic red pulp. (c) Percentage of myeloid/histiocyte antigen-positive cells among nucleated cells in the bone marrow. (d) Percentage of CD18-positive cells among nucleated cells in the bone marrow.
Fig. 2
Fig. 2
Spleen. (a) SPF cat. In the red pulp, a few cells express the myeloid/histiocyte antigen. F = follicle. Peroxidase anti-peroxidase method. Papanicolaou's haematoxylin counterstain. Bar = 100 μm. (b) Cat with FIP. In the red pulp, the vast majority of nucleated cells express the myeloid/histiocyte antigen. Peroxidase anti-peroxidase method. Papanicolaou's haematoxylin counterstain. Bar = 100 μm. (c) SPF cat. In the red pulp, a few cells express CD18. In the follicle, CD18 expression is restricted to a few cells in the center (follicular dendritic cells). Avidin–biotin peroxidase complex method. Papanicolaou's haematoxylin counterstain. Bar = 100 μm. (d) Cat with FIP. In the red pulp, the vast majority of nucleated cells express CD18. In the follicle, CD18 expression is restricted to a few cells in the center (follicular dendritic cells). Avidin–biotin peroxidase complex method. Papanicolaou's haematoxylin counterstain. Bar = 100 μm. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)
Fig. 3
Fig. 3
Cat with FIP. Mesenteric lymph node. Severe sinus histiocytosis. Sinus histiocytes exhibit strong expression of CD18 which is often most intense in the cell periphery. Avidin–biotin peroxidase complex method. Papanicolaou's haematoxylin counterstain. Bar = 100 μm.
Fig. 4
Fig. 4
Bone marrow. (a) SPF cat. Numerous scattered myeloid cells exhibit faint expression of CD18. (b) Cat with FIP. The majority of myeloid cells exhibit strong expression of CD18. Avidin–biotin peroxidase complex method. Papanicolaou's haematoxylin counterstain. Bars = 50 μm.
Fig. 5
Fig. 5
Box and Whisker plots, demonstrating levels of cytokine transcription in SPF cats, FCoV-infected cats without FIP and cats with FIP. The amount of target was calculated by 2−ΔCT, resulting in evaluation of the experimental samples as an n-fold difference relative to the calibrator fGAPDH (Kipar et al., 2001b). The plots display the range of values, the minimum and maximum, low (first) and high (third) quartiles and the median. (a) Cytokine transcription levels in the spleen; group: (1) SPF cats, (2) FCoV-infected cats without FIP, (3) cats with FIP; (b) cytokine transcription levels in mesenteric lymph nodes; group: (1) SPF cats, (2) FCoV-infected cats without FIP, (3) cats with FIP; (c) cytokine transcription levels in bone marrow; group: (1) SPF cats, (2) FCoV-infected cats without FIP, (3) cats with FIP.
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