Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?

Malbon, Alexandra; Meli, Marina L.; Barker, Emi; Davidson, AD; Tasker, Séverine; Kipar, Anja

doi:10.1016/j.jcpa.2018.11.001

Cited by 24 publications

(48 citation statements)

References 51 publications

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“…Pro-inflammatory cytokines and antiviral-related genes such as MX1, viperin and IFNγ have also been observed in tissues harvested from FCoV-infected cats with FIP [46]. In addition, recent reports focused on gene expression profiles from mesenteric or peritoneal macrophages harvested from cats with FIP revealed expression of pattern recognition receptors including toll, NOD and RIG-like receptors, pro-apoptotic genes, and genes related to differentiation of M1 macrophages in contrast to reduced expression of MCH class II receptor genes [47,48]. Lastly, the role of host anti-inflammatory factors such as regulatory T cells and IL-10 as well as innate factors such as natural killer cells factors warrant further examination based on other recent reports [29,49].…”

Section: Discussionmentioning

confidence: 99%

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

et al. 2019

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Background Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. Results Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. Conclusions In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.

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Section: Discussionmentioning

confidence: 99%

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

et al. 2019

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“…We then used a palette of methods on selected cases to confirm translation and identify the cell source of the cytokines. In light of both our previous findings in lymphatic tissues [20,21] and the importance of these cytokines in determining the balance of the immune response (Th1 vs. Th2/pro-vs. anti-inflammatory [32,33]), we also evaluated the hepatic IL-10 and IL-12p40 mRNA levels in an attempt to assess whether this ratio correlated with the clinical picture.…”

Section: Introductionmentioning

confidence: 76%

“…Despite being archetypally pro-inflammatory, at high concentrations IL-12 can inhibit the immune response and the generation of cytotoxic T lymphocytes [62,63]. In contrast to the liver, the mesenteric lymph nodes were previously found to downregulate IL-12 transcription in FIP, with IL-10 levels unaffected [20,21]. It would appear that neither high IL-12 nor high IL-10 are themselves protective and indeed plasmids encoding IL-12 have been found to enhance susceptibility to disease in FIPV vaccination studies, rather than offering protection as had been predicted [64].…”

Section: Discussionmentioning

confidence: 99%

“…In turn TNF-α functions as a possible contributor to the lymphocyte apoptosis observed in FIP [18,19]. Despite this, in natural disease, end stage FIP is associated with only a low increase or in some cases even a decrease in TNF-α transcription in the lymphatic tissues themselves [20,21]. In conjunction, IL-1β and IL-6 transcription showed no to low increases in the lymphatic tissues in FIP whilst IL-10 and IL-12 decreased or remained unchanged [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Feline Infectious Peritonitis as a Systemic Inflammatory Disease: Contribution of Liver and Heart to the Pathogenesis

Malbon

Fonfara

Meli

et al. 2019

Viruses

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Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of cats, induced by feline coronavirus (FCoV). A combination of as yet poorly understood host and viral factors combine to cause a minority of FCoV-infected cats to develop FIP. Clinicopathological features include fever, vasculitis, and serositis, with or without effusions; all of which indicate a pro-inflammatory state with cytokine release. As a result, primary immune organs, as well as circulating leukocytes, have thus far been of most interest in previous studies to determine the likely sources of these cytokines. Results have suggested that these tissues alone may not be sufficient to induce the observed inflammation. The current study therefore focussed on the liver and heart, organs with a demonstrated ability to produce cytokines and therefore with huge potential to exacerbate inflammatory processes. The IL-12:IL-10 ratio, a marker of the immune system's inflammatory balance, was skewed towards the pro-inflammatory IL-12 in the liver of cats with FIP. Both organs were found to upregulate mRNA expression of the inflammatory triad of cytokines IL-1β, IL-6, and TNF-α in FIP. This amplifying step may be one of the missing links in the pathogenesis of this enigmatic disease.2 of 17 distribution of organ lesions. The development of FIP lesions is triggered by activated, virus infected monocytes. In the presence of a generalised activation of venous endothelial cells, these monocytes induce the granulomatous phlebitis that is considered to be the first and hallmark lesion and can occur in a range of organs [4]. Endothelial cell activation, together with other systemic changes such as fever, indicates excessive systemic cytokine release though the precise sources remain unclear [4][5][6].Pro-inflammatory cytokines are the main mediators of the innate immune response, allowing communication between and priming of the various components of the innate immune system, e.g., activation of leukocytes and endothelial cells (reviewed by [6,7]). In cats, interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α are the main mediators of the acute phase inflammatory response [8] and cats with FIP exhibit clear clinical and histological evidence of overt inflammatory processes. Despite this, there are conflicting results on the presence and systemic levels of these cytokines in FIP. Early studies found high IL-1 and IL-6 activity in sera, ascitic fluid, and the supernatant of cultured peritoneal exudate cells of cats with FIP [9,10]. However, IL-6 mRNA levels in peripheral blood mononuclear cells (PBMC) were found to be unaltered, only mildly increased, or variable in FIP [11][12][13], whilst IL-10 and IL-12 transcription was markedly depressed [11].

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“…For FCoV, the ability to infect, replicate in and activate monocytes and macrophages is essential in the pathogenesis of feline infectious peritonitis (FIP), a fatal disease of felids. While the low-virulence feline enteric coronavirus (FECV) biotype primarily replicates in enterocytes and does only induce mild enteric disease, the highly virulent feline infectious peritonitis virus (FIPV) biotype predominantly arises after S gene mutations in FECV of the infected host that allow efficient replication in and systemic spread with monocytes (58). This allows rapid dissemination of the virus throughout the body (monocyte-associated viremia) and is a prerequisite of the monocyte activation with subsequent development of the granulomatous phlebitis that is the hallmark of FIP (55, 59, 60).…”

Section: Discussionmentioning

confidence: 99%

Python nidoviruses, more than respiratory pathogens

Dervas

Hepojoki

Smura

et al. 2020

Preprint

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28In recent years nidoviruses have emerged as an important respiratory pathogen of reptiles, 29 affecting especially captive python populations. In pythons, nidovirus infection induces an 30 inflammation of the upper respiratory and alimentary tract which can develop into a severe and 31 often fatal proliferative pneumonia. We observed pyogranulomatous and fibrinonecrotic lesions 32 in organ systems other than the respiratory tract during full post mortem examinations on 30 33 nidovirus RT-PCR positive pythons of varying species originating from Switzerland and Spain. 34The observations prompted us to study whether the atypical tissue tropism associates with 35 previously unknown nidoviruses or changes in the nidovirus genome. RT-PCR and inoculation 36 of Morelia viridis cell cultures served to recruit the cases and to obtain virus isolates. 37 Immunohistochemistry and immunofluorescence staining against nidovirus nucleoprotein 38 demonstrated that the virus not only infects a broad spectrum of epithelial (respiratory and 39 alimentary epithelium, hepatocytes, renal tubules, pancreatic ducts etc.), but also intravascular 40 monocytes, intralesional macrophages and endothelial cells. By next-generation sequencing we 41 obtained full length genome for a novel nidovirus species circulating in Switzerland. Analysis of 42 viral genomes recovered from pythons showing nidovirus infection-associated respiratory or 43 systemic disease did not explain the observed phenotypes. The results indicate that python 44 nidoviruses have a broad cell and tissue tropism, further suggesting that the course of infection 45 could vary and involve lesions in a broad spectrum of tissues and organ systems as a 46 consequence of monocyte-mediated systemic spread of the virus. 47 IMPORTANCE 49During the last years, python nidoviruses have become a primary cause of fatal disease in 50 pythons. Nidoviruses represent a threat to captive snake collections, as they spread rapidly and 51 can be associated with high morbidity and mortality. Our study indicates that, different from 52 previously evidence, the viruses do not only affect the respiratory tract, but can spread in the 53 entire body with blood monocytes, have a broad spectrum of target cells, and can induce a 54 variety of lesions. Nidovirales is an order of animal and human viruses that compromise 55 important zoonotic pathogens such as MERS-CoV and SARS-CoV, as well as the recently 56 emerged SARS-CoV-2. Python nidoviruses belong to the same subfamily as the mentioned 57 human viruses and show similar characteristics (rapid spread, respiratory and gastrointestinal 58 tropism, etc.). The present study confirms the relevance of natural animal diseases to better 59 understand the complexity of viruses of the order nidovirales.

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Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?

Cited by 24 publications

References 51 publications

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

Feline Infectious Peritonitis as a Systemic Inflammatory Disease: Contribution of Liver and Heart to the Pathogenesis

Python nidoviruses, more than respiratory pathogens

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