Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis

Valerie Hughes (Corresponding Author), Jim McNair, Samuel Strain, Claire Barry, Joyce McLuckie, Mintu Nath, George Caldow, Karen Stevenson

Research output: Contribution to journalArticle

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Abstract

Johne's disease (JD), is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). Diagnosis of subclinical JD is problematic as test sensitivity is limited. Th1 responses to Map are activated early, thus detection of a cell-mediated response, indicated by measuring interferon gamma (IFN-γ) stimulated by mycobacterial antigens, may give the first indication of sub-clinical infection. Crude extracts of Map (PPDJ) have been used to detect the cell-mediated response in infected cattle. More specific, quantifiable antigens may improve test specificity and reproducibility. Map-specific proteins, MAP_3651c and MAP_0268c, raised a cell-mediated immune response in sub-clinically infected sheep. Results presented in this manuscript demonstrate these proteins elicit a cell-mediated response in experimental and natural infections of cattle. Individual ranked IFN-γ responses of experimentally infected calves to PPDJ showed a high, statistically significant association with ranked responses of recombinant Map antigens. Responses of infected animals were higher than the control group. Threshold values determined using data from an experimental infection were applied to naturally infected animals. Some animals exhibited responses above these threshold values. Responses to MAP_3651c on a farm categorised as high-risk for JD showed strong evidence (P<0.001) that responses were significantly different to lower-risk farms. The IGRA test may prove to be an additional tool for the diagnosis of JD, and inclusion of specific antigens a refinement however, understanding and interpretation of IGRA results remain challenging and further investigation will be required to determine whether the IGRA test can detect exposure and hence predict clinical JD.

Original languageEnglish
Pages (from-to)244-253
Number of pages10
JournalResearch in Veterinary Science
Volume114
Early online date29 Apr 2017
DOIs
Publication statusPublished - Oct 2017

Fingerprint

Mycobacterium avium subsp. paratuberculosis
Paratuberculosis
paratuberculosis
Proteome
proteome
interferon-gamma
Recombinant Proteins
recombinant proteins
Interferon-gamma
Mycobacterium avium
cattle
Antigens
Infection
antigens
Enteritis
Complex Mixtures
animal behavior
infection
Sheep
Proteins

Keywords

  • Animals
  • Bacterial Proteins/metabolism
  • Cattle
  • Cattle Diseases/immunology
  • Immunity, Cellular
  • Interferon-gamma/pharmacology
  • Paratuberculosis/immunology
  • Proteome
  • Recombinant Proteins/metabolism

Cite this

Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis. / Hughes, Valerie (Corresponding Author); McNair, Jim; Strain, Samuel; Barry, Claire; McLuckie, Joyce; Nath, Mintu; Caldow, George; Stevenson, Karen.

In: Research in Veterinary Science, Vol. 114, 10.2017, p. 244-253.

Research output: Contribution to journalArticle

Hughes, Valerie ; McNair, Jim ; Strain, Samuel ; Barry, Claire ; McLuckie, Joyce ; Nath, Mintu ; Caldow, George ; Stevenson, Karen. / Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis. In: Research in Veterinary Science. 2017 ; Vol. 114. pp. 244-253.
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abstract = "Johne's disease (JD), is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). Diagnosis of subclinical JD is problematic as test sensitivity is limited. Th1 responses to Map are activated early, thus detection of a cell-mediated response, indicated by measuring interferon gamma (IFN-γ) stimulated by mycobacterial antigens, may give the first indication of sub-clinical infection. Crude extracts of Map (PPDJ) have been used to detect the cell-mediated response in infected cattle. More specific, quantifiable antigens may improve test specificity and reproducibility. Map-specific proteins, MAP_3651c and MAP_0268c, raised a cell-mediated immune response in sub-clinically infected sheep. Results presented in this manuscript demonstrate these proteins elicit a cell-mediated response in experimental and natural infections of cattle. Individual ranked IFN-γ responses of experimentally infected calves to PPDJ showed a high, statistically significant association with ranked responses of recombinant Map antigens. Responses of infected animals were higher than the control group. Threshold values determined using data from an experimental infection were applied to naturally infected animals. Some animals exhibited responses above these threshold values. Responses to MAP_3651c on a farm categorised as high-risk for JD showed strong evidence (P<0.001) that responses were significantly different to lower-risk farms. The IGRA test may prove to be an additional tool for the diagnosis of JD, and inclusion of specific antigens a refinement however, understanding and interpretation of IGRA results remain challenging and further investigation will be required to determine whether the IGRA test can detect exposure and hence predict clinical JD.",
keywords = "Animals, Bacterial Proteins/metabolism, Cattle, Cattle Diseases/immunology, Immunity, Cellular, Interferon-gamma/pharmacology, Paratuberculosis/immunology, Proteome, Recombinant Proteins/metabolism",
author = "Valerie Hughes and Jim McNair and Samuel Strain and Claire Barry and Joyce McLuckie and Mintu Nath and George Caldow and Karen Stevenson",
note = "This work was mostly funded by The Scottish Government, Rural and Environment Science and Analytical Services Division (RESAS) and the European Union (‘ParaTBtools’ contract number: FOOD-CT-2006-023106). The authors would particularly like to acknowledge the contribution of Douwe Bakker, both as co-ordinator of ParaTBtools and for the kind gift of PPDJ which has proved invaluable in this and other studies. In addition, parts of this work were funded by Quality Meat Scotland, and Genecom. The authors gratefully acknowledge the following people who facilitated this study: Linda May; Susan Denham- staff of the Mycobacteria group, Moredun, for excellent technical assistance; Sarah Brocklehurst, BIOSS, for reading the manuscript and offering helpful comments and suggestions regarding statistical analysis; Staff of Bioservices, Moredun, for sample collection and animal husbandry; Dr. Colin Penny, SRUC, for sourcing animals infected with Map; Farmers and their stockmen for animal management and graciously allowing us to sample animals on their farm.",
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T1 - Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis

AU - Hughes, Valerie

AU - McNair, Jim

AU - Strain, Samuel

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AU - McLuckie, Joyce

AU - Nath, Mintu

AU - Caldow, George

AU - Stevenson, Karen

N1 - This work was mostly funded by The Scottish Government, Rural and Environment Science and Analytical Services Division (RESAS) and the European Union (‘ParaTBtools’ contract number: FOOD-CT-2006-023106). The authors would particularly like to acknowledge the contribution of Douwe Bakker, both as co-ordinator of ParaTBtools and for the kind gift of PPDJ which has proved invaluable in this and other studies. In addition, parts of this work were funded by Quality Meat Scotland, and Genecom. The authors gratefully acknowledge the following people who facilitated this study: Linda May; Susan Denham- staff of the Mycobacteria group, Moredun, for excellent technical assistance; Sarah Brocklehurst, BIOSS, for reading the manuscript and offering helpful comments and suggestions regarding statistical analysis; Staff of Bioservices, Moredun, for sample collection and animal husbandry; Dr. Colin Penny, SRUC, for sourcing animals infected with Map; Farmers and their stockmen for animal management and graciously allowing us to sample animals on their farm.

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N2 - Johne's disease (JD), is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). Diagnosis of subclinical JD is problematic as test sensitivity is limited. Th1 responses to Map are activated early, thus detection of a cell-mediated response, indicated by measuring interferon gamma (IFN-γ) stimulated by mycobacterial antigens, may give the first indication of sub-clinical infection. Crude extracts of Map (PPDJ) have been used to detect the cell-mediated response in infected cattle. More specific, quantifiable antigens may improve test specificity and reproducibility. Map-specific proteins, MAP_3651c and MAP_0268c, raised a cell-mediated immune response in sub-clinically infected sheep. Results presented in this manuscript demonstrate these proteins elicit a cell-mediated response in experimental and natural infections of cattle. Individual ranked IFN-γ responses of experimentally infected calves to PPDJ showed a high, statistically significant association with ranked responses of recombinant Map antigens. Responses of infected animals were higher than the control group. Threshold values determined using data from an experimental infection were applied to naturally infected animals. Some animals exhibited responses above these threshold values. Responses to MAP_3651c on a farm categorised as high-risk for JD showed strong evidence (P<0.001) that responses were significantly different to lower-risk farms. The IGRA test may prove to be an additional tool for the diagnosis of JD, and inclusion of specific antigens a refinement however, understanding and interpretation of IGRA results remain challenging and further investigation will be required to determine whether the IGRA test can detect exposure and hence predict clinical JD.

AB - Johne's disease (JD), is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). Diagnosis of subclinical JD is problematic as test sensitivity is limited. Th1 responses to Map are activated early, thus detection of a cell-mediated response, indicated by measuring interferon gamma (IFN-γ) stimulated by mycobacterial antigens, may give the first indication of sub-clinical infection. Crude extracts of Map (PPDJ) have been used to detect the cell-mediated response in infected cattle. More specific, quantifiable antigens may improve test specificity and reproducibility. Map-specific proteins, MAP_3651c and MAP_0268c, raised a cell-mediated immune response in sub-clinically infected sheep. Results presented in this manuscript demonstrate these proteins elicit a cell-mediated response in experimental and natural infections of cattle. Individual ranked IFN-γ responses of experimentally infected calves to PPDJ showed a high, statistically significant association with ranked responses of recombinant Map antigens. Responses of infected animals were higher than the control group. Threshold values determined using data from an experimental infection were applied to naturally infected animals. Some animals exhibited responses above these threshold values. Responses to MAP_3651c on a farm categorised as high-risk for JD showed strong evidence (P<0.001) that responses were significantly different to lower-risk farms. The IGRA test may prove to be an additional tool for the diagnosis of JD, and inclusion of specific antigens a refinement however, understanding and interpretation of IGRA results remain challenging and further investigation will be required to determine whether the IGRA test can detect exposure and hence predict clinical JD.

KW - Animals

KW - Bacterial Proteins/metabolism

KW - Cattle

KW - Cattle Diseases/immunology

KW - Immunity, Cellular

KW - Interferon-gamma/pharmacology

KW - Paratuberculosis/immunology

KW - Proteome

KW - Recombinant Proteins/metabolism

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DO - 10.1016/j.rvsc.2017.04.018

M3 - Article

VL - 114

SP - 244

EP - 253

JO - Research in Veterinary Science

JF - Research in Veterinary Science

SN - 0034-5288

ER -