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The Pirbright Institute publication directory contains details of selected publications written by our researchers.

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Montoya M, Schiavoni G, Mattei F, Gresser I, Belardelli F, Borrow P, Tough D F (2002)

Type I interferons produced by dendritic cells promote their phenotypic and functional activation

Blood 99 (9), 3263-3271
Publisher’s version: http://dx.doi.org/10.1182/blood.V99.9.3263

Abstract

Resting dendritic cells (DCs) are resident in most tissues and can be activated by environmental stimuli to mature into potent antigen-presenting cells. One important stimulus for DC activation is infection; DCs can be triggered through receptors that recognize microbial components directly or by contact with infection-induced cytokines. We show here that murine DCs undergo phenotypic maturation upon exposure to type I interferons (type I IFNs) in vivo or in vitro. Moreover, DCs either derived from bone marrow cells in vitro or isolated from the spleens of normal animals express IFN-alpha and IFN-beta, suggesting that type I IFNs can act in an autocrine manner to activate DCs. Consistent with this idea, the ability to respond to type I IFN was required for the generation of fully activated DCs from bone marrow precursors, as DCs derived from the bone marrow of mice lacking a functional receptor for type I IFN had reduced expression of costimulatory and adhesion molecules and a diminished ability to stimulate naive T-cell proliferation compared with DCs derived from control bone marrow. Furthermore, the addition of neutralizing anti-IFN-alpha/beta antibody to purified splenic DCs in vitro partially blocked the "spontaneous" activation of these cells, inhibiting the upregulation of costimulatory molecules, secretion of IFN-gamma, and T-cell stimulatory activity. These results show that DCs both secrete and respond to type I IFN, identifying type I interferons as autocrine DC activators.
Postigo M, Bell-Sakyi L, Paxton E, Sumption K (2002)

Kinetics of experimental infection of sheep with Ehrlichia ruminantium cultivated in tick and mammalian cell lines

Experimental and Applied Acarology 28 (1), 187-193
Publisher’s version: http://dx.doi.org/10.1023/a:1025390215007

Abstract

Inoculation of sheep with Ehrlichia (previously Cowdria) ruminantium which has been cultivated in mammalian endothelial cell cultures is almost always followed by a severe clinical reaction, whereas inoculation of the agent cultivated in tick cell lines usually does not provoke a clinical response, but may result in seroconversion and/or protection against subsequent challenge with virulent stabilates. A quantitative, real-time PCR assay was developed to determine the kinetics of infection (rickettsaemia) in sheep inoculated with tick cell- and mammalian cell- derived E. ruminantium (Gardel isolate). The method and initial results are described, and the significance of the findings is discussed in relation to the clinical responses of the sheep.
Rhodes S G, Graham S P (2002)

Is ‘timing’ important for cytokine polarization?

Trends in Immunology 23 (5), 246-249
Publisher’s version: http://dx.doi.org/10.1016/S1471-4906(02)02200-7

Abstract

A comparison of the longitudinal cytokine responses of cattle to infection with intracellular Mycobacterium bovis and extracellular Onchocerca ochengi illustrates the development of reciprocal interferon-? and interleukin-4 responses, which result ultimately in an infection-induced type-1 or type-2 polarization, respectively. These kinetic studies of natural host–pathogen relationships show that the cytokine responses to infection fluctuate over time, resulting in periods of polarization and nonpolarization before the establishment of a chronic infection. Here, we discuss our data from cattle in the light of the current understanding of cytokine polarization towards infection in mouse models and humans.
Salguero F J, Ruiz-Villamor E, Bautista M J, Sanchez-Cordon P J, Carrasco L, Gomez-Villamandos J C (2002)

Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines

Veterinary Immunology and Immunopathology 90 (1-2), 11-22
Publisher’s version: http://dx.doi.org/10.1016/s0165-2427(02)00225-8

Abstract

To gain further insight into the pathogenesis of African swine fever (ASF), the cytokine expression by macrophages in spleen and lymph nodes were examined. Twenty-one piglets were inoculated with the highly virulent isolate Spain-70 of ASF virus and killed in groups at 1-7 post-inoculation days (pid). An increase in the immunohistochemical detection of proinflammatory monokines in spleen and renal and gastrohepatic lymph nodes is reported, along with an increase in the serum levels of TNF-alpha and IL-1beta. The expression of these cytokines is detected simultaneously in time and space with the viral protein 73 (vp73) of the ASF virus detection. Our results demonstrate that mononuclear phagocyte system cell activation results in the release of several cytokines that could induce apoptosis of lymphocytes and haemodynamic changes.
Salguero F J, Sanchez-Cordon P J, Nunez A, Gomez-Villamandos J C (2002)

Histopathological and ultrastructural changes associated with herpesvirus infection in waterfowl

Avian Pathology 31 (2), 133-140
Publisher’s version: http://dx.doi.org/10.1080/03079450120118612

Abstract

Duck virus enteritis is an acute contagious viral disease affecting birds of the order Anseriformes (ducks, geese and swans). The disease agent is a member of the Herpesviridae family (Anatidae herpes virus 1). A group of Anseriformes waterfowl from a Nature Reserve and Centre for the Recovery of Endangered Species in Spain suffered an outbreak of the disease, affecting adults, young and newborns. Other non-Anseriformes waterfowl such as coots, from the family Rallidae, order Gruiformes, were also affected. Histopathological and ultrastructural findings confirmed the viral infection. The present study provides evidence that birds different from the order Anseriformes can be affected, suggesting that the virus has the ability to infest other non-Anseriformes waterfows.
Sanchez-Cordon P J, Hervas J, de Lara F C, Jahn J, Salguero F J, Gomez-Villamandos J C (2002)

Reovirus infection in psittacine birds (Psittacus erithacus): Morphologic and immunohistochemical study

Avian Diseases 46 (2), 485-492
Publisher’s version: http://dx.doi.org/10.1637/0005-2086(2002)046[0485:riipbp]2.0.co;2

Abstract

In this paper we report on an outbreak of reovirus, herpesvirus (Pacheco disease), and/or mycosis infection (Aspergillus spp. and Zygomyces spp.) affecting a batch of young African grey parrots (Psittacus erithacus), with 80% morbidity and 30% mortality. Study material was taken from five birds (four dead and one euthanatized) with a range of clinical symptoms (depression, diarrhea, respiratory symptoms). Diagnosis was confirmed by immunohistochemical detection of avian reovirus, electron microscopy, and virus isolation. Viral antigen of reovirus was detected mainly in large mononuclear cells in the bursa of Fabricius and the spleen, pancreas epithelia-l cells, and circulating cells; lymphoid organs displayed the largest number of immunopositive cells and severe lymphocyte depletion. Bacteriologic study was negative. Reovirus infection was common in all birds studied, whereas Pacheco disease and mycosis were found in only some, suggesting that reovirus could be the initial cause triggering the outbreak and facilitating infection by other agents and their swift spread through the batch.
Sanchez-Cordon P J, Salguero F J, Nunez A, Gomez-Villamandos J C, Carrasco L O (2002)

Glomerulonephritis associated with simultaneous canine adenovirus-1 and Dirofilaria immitis infection in a dog

Journal of Veterinary Medicine Series B-Infectious Diseases and Veterinary Public Health 49 (5), 235-239
Publisher’s version: http://dx.doi.org/10.1046/j.1439-0450.2002.00554.x

Abstract

This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2-year-old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.
Tchilian E Z, Beverley P C L (2002)

CD45 in memory and disease

Archivum Immunologiae et Therapiae Experimentalis 50 (2), 85-93
Publisher’s version: http://www.aite.wroclaw.pl/files/AITEFullText/50z201.pdf

Abstract

CD45 (the leukocyte common antigen) is known to function as a tyrosine phosphatase in leukocyte signaling. Biochemical studies indicate that CD45 is involved in the regulation both of T cell receptor-associated kinases and Janus kinases that transmit signals from cytokine receptors. However, the function of the different isoforms of CD45 generated by complex alternative splicing, and indeed the role of the whole extracellular domain of the molecule, remain mysterious. Analysis of CD45 knock-outs and of transgenic mice expressing single CD45 isoforms, as well as the disease associations of human polymorphisms, is providing new insights into CD45 function. Accumulating data from these genetic and biochemical studies promises to elucidate the role of high and low molecular weight isoforms of CD45 in the function of naive and memory T lymphocytes.
Weber F, Bridgen A, Fazakerley J K, Streitenfeld H, Kessler N, Randall R E, Elliott R M (2002)

Bunyamwera Bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon

Journal of Virology 76 (16), 7949-7955
Publisher’s version: http://dx.doi.org/10.1128/jvi.76.16.7949-7955.2002

Abstract

Production of alpha/beta interferons (IFN-?/?) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-?/?, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-?B and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-?/? system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-?/? in order to increase the virulence of Bunyamwera virus.

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