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

Hughes, Valerie; McNair, J.; Strain, S.; Barry, Claire; McLuckie, Joyce; Nath, Mintu; Caldow, George; Stevenson, Karen

doi:10.1016/j.rvsc.2017.04.018

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…The protein antigen Map 1365, which had been shown to induce a marked IFN-γ response in 5/7 sub-clinically infected sheep (15), elicited only very low IFN-γ levels and was not discriminatory in goats. Based on results from sheep and cattle, Map 0268c was suggested to have the ability to discriminate groups of infected and uninfected animals (15,16). Two preparations of this antigen were tested here and, although one of the preparations stimulated increased IFNγ release of blood cells of individual goats, they did not enable discrimination between the treatment groups.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown to have the ability to discriminate groups of infected and uninfected sheep (15) and to elicit increased IFNγ levels in cattle from paraTb high-risk farms (16). Two different recombinant antigen preparations of Map 3651c were included in the present study, a full lengths antigen, Map 3651c (21,36) and a truncated protein, Map 3651cT(it) (16). Obviously, the capacity of the truncated protein to induce IFN-γ responses was reduced compared to the full lengths antigen, which may be due to altered epitope configuration.…”

Section: Discussionmentioning

confidence: 99%

“…During recent years, several recombinant proteins or peptides derived from MAP were evaluated in experimental and field studies using cattle and sheep in an attempt to replace PPDj with more specific antigens (12)(13)(14)(15)(16)(17)(18). Promising protein antigen candidates have been identified, for example Map 3651c and Map 0268c.…”

Section: Introductionmentioning

confidence: 99%

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Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

et al. 2021

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Despite its potential for early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) infection, the IFN-γ release assay is not used routinely, because of low specificity of the established crude antigen preparation Johnin (PPDj). Limited data are available assessing the potential of MAP-derived protein and lipopeptide antigens to replace PPDj in assays for goats, while cattle and sheep have been studied more extensively. Furthermore, MAP infection is claimed to interfere with the diagnosis of bovine tuberculosis when other crude antigen preparations (PPDb, PPDa) are applied. In this study, the diagnostic potential of MAP-derived recombinant protein antigens, synthetic MAP lipopentapeptides and of Mycobacterium bovis-specific peptide cocktails was assessed compared to crude mycobacterial antigen preparations in experimentally infected goats. Goats were inoculated with MAP, or Mycobacterium avium subsp. hominissuis (MAH) as surrogate for environmental mycobacteria, non-exposed animals served as controls. Mycobacterium avium Complex-specific antibody and PPDj-induced IFN-γ responses were monitored in vivo. Infection status was assessed by pathomorphological findings and bacteriological tissue culture at necropsy 1 year after inoculation. The IFN-γ response to 13 recombinant protein antigens of MAP, two synthetic MAP lipopentapeptides and three recombinant peptide cocktails of Mycobacterium bovis was investigated at three defined time points after infection. At necropsy, MAP or MAH infection was confirmed in all inoculated goats, no signs of infection were found in the controls. Antibody formation was first detected 3–6 weeks post infection (wpi) in MAH-inoculated and 11–14 wpi in the MAP-inoculated goats. Maximum PPDj-induced IFN-γ levels in MAH and MAP exposed animals were recorded 3–6 and 23–26 wpi, respectively. Positive responses continued with large individual variation. Antigens Map 0210c, Map 1693c, Map 2020, Map 3651cT(it), and Map 3651c stimulated increased whole blood IFN-γ levels in several MAP-inoculated goats compared to MAH inoculated and control animals. These IFN-γ levels correlated with the intensity of the PPDj-induced responses. The two synthetic lipopentapeptides and the other MAP-derived protein antigens had no discriminatory potential. Stimulation with Mycobacterium bovis peptide cocktails ESAT6-CFP10, Rv3020c, and Rv3615c did not elicit IFN-γ production. Further work is required to investigate if test sensitivity will increase when mixtures of the MAP-derived protein antigens are applied.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

et al. 2021

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“…These aspects, related to the performance of PPDJs and the robustness of IC validation, could be improved by enrolling more animals in future investigations. In addition, a further evolution of our study could be the use of recombinant antigens, peptides, or proteins from MAP, to increase the Sp of the IFN-γ test (97). These antigens have already been widely used in the IFN-γ test for the diagnosis of bTB in bovines (98,99) and buffalo (92), and the most widely used antigens are ESAT6/CFP10, or other antigen cocktails, with the aim of increasing the Sp of the IFN-γ test.…”

Section: Discussionmentioning

confidence: 99%

Early Detection of Mycobacterium avium subsp. paratuberculosis Infected Cattle: Use of Experimental Johnins and Innovative Interferon-Gamma Test Interpretative Criteria

et al. 2021

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Paratuberculosis (PTB), also known as Johne's disease, is a chronic proliferative enteritis of ruminants caused by Mycobacterium avium subsp.paratuberculosis (MAP). To date, PTB diagnosis, based on serology, fecal culture, and real-time polymerase chain reaction, has identified animals in advanced stages of infection. To detect MAP infection in animals earlier, the interferon-gamma (IFN-γ) test may be applied. This assay detects cytokines produced by T-lymphocytes of infected subjects after stimulation with purified protein derivatives (PPDs), extracted from Mycobacterium bovis (MB) and from M. avium (MA). The study involved three bovine herds: one PTB-infected herd, one PTB-free herd, and one with an outbreak of bovine tuberculosis. The IFN-γ test was performed on 235 animals, using bovine PPD (PPDB), avian PPD (PPDA), and three experimental PPD Johnins (PPDJs) extracted from a synthetic liquid medium culture of MAP (PPDJ A, B, and C), to assess early MAP detection and avoid false reactions to MB. Furthermore, IFN-γ results were evaluated using 12 interpretative criteria (ICs), based on the differences and ratio between PPD optical density (OD) and IFN-γ basal OD values after lymphocytic stimulation. IC accuracy was expressed as area under the receiver operating characteristic curve. Through a longitudinal study, PPDJs proved to be specific and sensitive in the detection of MAP-infected animals. Among the evaluated ICs, six showed the best performance in terms of accuracy (p < 0.0001), highlighting PTB subclinical infections. In particular, the two best criteria reached sensitivity values of 100% [confidence interval (CI) 95%, 94.1–100%] with a specificity of 91.8% (CI 95%, 81.9–97.3%) and sensitivity levels of 80.6% (CI 95%, 69.1–89.2%) with a specificity of 100% (CI 95%, 94.1–100%). Thus, the IFN-γ assay proved to be a useful diagnostic tool to identify early subclinical MAP-infected animals, in order to manage infected cattle or those exposed to MAP and to monitor younger calves within a herd. Furthermore, the IFN-γ test can be considered an additional test to avoid the introduction of MAP-infected animals, especially in herds where disease has already been eradicated and preservation of the health status is required to maintain the PTB certification level.

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“…• Interferon Gamma (IFN-gamma): useful for the detection of young animals that are in the early stages of infection. The downside is its low specificity and high cost [19].…”

Section: Introductionmentioning

confidence: 99%

Bull and cow-level prevalence of paratuberculosis in Lidia’s cattle breed from the Azores

Pacheco-Lima¹,

Silva²,

Valadão³

et al. 2021

Anim Husb Dairy Vet Sci

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Mycobacterium avium subspecies paratuberculosis (MAP) causes paratuberculosis, also known as Johne's disease, in domestic ruminants and wild species, resulting in economic losses among farmed ruminants. In Portugal, the true herd-level prevalence of paratuberculosis is unknown and the disease is considered under diagnosed. Particularly in the Azores only a very few studies were developed reporting this infection considering the potential loss in milk production. The aim of the present study is to evaluate the incidence of bovine paratuberculosis in a Lidia bovine population called "Brava dos Acores", destined to the typical Azorean street bullfighting as well as the traditional equestrian bullfight (in the ring). For such purpose, 68 animals belonging to that bullfight population mainly females (n= 55 vs 13 males) aged between 7 to 223 months were submitted to a blood collection, via the coccygeal vein, for diagnostic of paratuberculosis through the Elisa diagnostic test. Results showed that, from the 68 studied animals, 63 were negative for the presence of Paratuberculosis, 4 were positive and 1 was doubtful. The percentage of infected animals with positive and doubtful animals was 7.4%.In addition to the new knowledge obtained, it was concluded that further studies on this breed will be essential to expand the existing information.

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

Cited by 8 publications

References 23 publications

Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

Early Detection of Mycobacterium avium subsp. paratuberculosis Infected Cattle: Use of Experimental Johnins and Innovative Interferon-Gamma Test Interpretative Criteria

Bull and cow-level prevalence of paratuberculosis in Lidia’s cattle breed from the Azores

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