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

V Hughes, J McNair, S Strain, C Barry, J McLuckie, M Nath, G Caldow, K Stevenson

Research output: Contribution to journalArticle

1 Citation (Scopus)

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
Volume144
Early online date29 Apr 2017
DOIs
Publication statusFirst published - 29 Apr 2017

Fingerprint

paratuberculosis
proteome
interferon-gamma
recombinant proteins
Mycobacterium avium
cattle
antigens
animal behavior
infection
testing
farms
enteritis
cells
cell-mediated immunity
reproducibility
animals
proteins
calves
sheep
extracts

Keywords

  • Cell-mediated
  • Diagnosis
  • Interferon gamma release assay
  • Johne's
  • Mycobacterium avium subspecies
  • Paratuberculosis

Cite this

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title = "Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis",
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 = "Cell-mediated, Diagnosis, Interferon gamma release assay, Johne's, Mycobacterium avium subspecies, Paratuberculosis",
author = "V Hughes and J McNair and S Strain and C Barry and J McLuckie and M Nath and G Caldow and K Stevenson",
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doi = "10.1016/j.rvsc.2017.04.018",
language = "English",
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journal = "Research in Veterinary Science",
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Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis. / Hughes, V; McNair, J; Strain, S; Barry, C; McLuckie, J; Nath, M; Caldow, G; Stevenson, K.

In: Research in Veterinary Science, Vol. 144, 29.04.2017, p. 244 - 253.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gamma interferon responses to proteome-determined specific recombinant proteins in cattle experimentally- and naturally-infected with paratuberculosis

AU - Hughes, V

AU - McNair, J

AU - Strain, S

AU - Barry, C

AU - McLuckie, J

AU - Nath, M

AU - Caldow, G

AU - Stevenson, K

PY - 2017/4/29

Y1 - 2017/4/29

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 - Cell-mediated

KW - Diagnosis

KW - Interferon gamma release assay

KW - Johne's

KW - Mycobacterium avium subspecies

KW - Paratuberculosis

U2 - 10.1016/j.rvsc.2017.04.018

DO - 10.1016/j.rvsc.2017.04.018

M3 - Article

VL - 144

SP - 244

EP - 253

JO - Research in Veterinary Science

JF - Research in Veterinary Science

SN - 0034-5288

ER -