University of Otago

Disease Research Lab (DRL)

Research Overview

DRL has been carrying out research on mycobacterial diseases (tuberculosis/paratuberculosis) in ruminants and wildlife species for the past 35 years. In the past decade our work has led to the development of improved immunodiagnostics and molecular techniques for the detection of paratuberculosis (Johnes disease). DRL has recently identified deer breeds with polarised phenotypes for resistance and susceptability to paratuberculosis.

DRL Activities

Research Projects

Johne's disease

 

Researchers:

Johne's disease (Paratuberculosis)

DRL research is currently focused on exploring immune mechanisms that are associated with either pathological (diagnostic) or protective responses in deer exposed to M.paratuberculosis. Purebred lines of deer that display extremes of resistance or susceptibility to paratuberculosis are being studied to identify candidate genes that result in a resistant (R) or susceptable (S) phenotype In vivo & in vitro. Transcriptomics on mononuclear cells studies on deer with either R or S genotypes are being carried out currently.

Objectives of current studies

  • Characterise pathways of  immunepathogenesis in experimentally infected deer displaying different stages of Johne's disease

  • Identify immune markers associated with protective immunity in animals with resistant genotypes.

  • Map genes associated with resistance or susceptable deer phenotypes.

These projects have  involved collaboration with researchers at AgResearch (Invermay and Wallaceville). Important key relationships have been formed with the end users who are supporting these programmes with co-funding and access to unique deer breeds. Government support is through the Foundation for Research Science and Technology (FoRST) and the Johnes Disease Research Consortium (JDRC).

References:

O'Brien R, Hughes A, Liggett S, Griffin F. Composite testing for ante-mortem diagnosis of Johne's disease in farmed New Zealand deer: correlations between reactivity and faecal shedding as determined by quantitative PCR. BMC veterinary Research 04/2013; 9(1):72. DOI: 10. 1186/1746-6148-9-72 pp72.

Dobson B, Liggett S, O'Brien R, Griffin JF. Innate immune markers that distinguish red deer (Cervus elaphus) selected for resistant or susceptible genotypes for Johne's disease.  Vet Res 2013 Jan 24;44(1):5.

Mackintosh, C.G., Clark, R.G., Thompson, B., Tolentino, B., de Lisle, G.W. and Griffin J.F.T. Immunological and pathological responses of red deer resistant or susceptible genoytpes, to experimental challenge with Mycobacterium avium subsp. paratuberculosis. Veterinary Microbiology, Volume 143, Issues 1–2, 15 September 2011, Pages 131-142

Robinson, M.W., O’Brien, R., Mackintosh, C.G., Clark, R.G. and Griffin, J.F.T. Immunoregulatory cytokines are associated with protection from immunopathology following Mycobacterium avium subspecies paratuberculosis infection in red deer. Infection and Immunity.  79(5): 2089–2097 (2011)

Mackintosh, C.G., Clark, R.G., Thompson, B., Tolentino, B., Griffin, J.F.T., de Lisle, G.W.  Age susceptibility of red deer (Cervus elaphus) to paratuberculosis. Veterinary Microbiology. 143, 255-261 (2010).

Pieterse, M. C., Eisenbergh, S. W. F., Folmer, G. E., Liggett, S., Griffin, J. F. T., Koets, A. P., Nielen, M. Evidence of Mycobacterium avium subsp. paratuberculosis infection in Dutch farmed red deer. Tijdschrift voor Diergeneeskunde. 135: 23, 886-890 (2010).

Dobson, B.J., Mackintosh, C.G., Griffin, J.F.T. Development of the thymus and peyer’s patches in the first year of life in red deer (Cervus elaphus) . Veterinary Immunology and Immunopathology. 137:93-98 (2010).

Robinson, M., O’Brien, R., Mackintosh, C.G., Griffin, J.F.T. Peripheral blood mononuclear cell population changes associated with age and Mycobacterium avium subspecies paratuberculosis infection in red deer (Cervus elaphus). Veterinary Immunology and Immunopathology. 136: 211-218 (2010).

Gillan, S., Hughes, A.D., O’Brien, R., Griffin, J.F.T. Ovine immune parameters following immunization against Mycobacterium avium ssp. paratuberculosis using a lipid-based live cell vaccine. Veterinary Immunology and Immunopathology. 137: 109-119 (2010)

Gillan, S., O’Brien, R., Hughes, A.D., Griffin, J.F.T. Identification of immune parameters to differentiate disease states among sheep infected with Mycobacterium avium ssp. paratuberculosis. Clinical and Vaccine Immunology 17: 108-117 (2010).

Clark, R.G., Griffin, J.F.T. and Mackintosh, C.G. Johne’s disease caused by Mycobacterium avium subsp paratuberculosis infection in red deer (Cervus elaphus): An histopathological grading system, and comparison of paucibacillary and multibacillary disease New Zealand Veterinary Journal 58: 90-97 (2010)

Griffin, J.F.T., Hughes, A.D., Liggett, S., Farquhar, P.A., Mackintosh, C.G. and Bakker, D. Efficacy of a novel lipid-formulated whole bacterial cell vaccine against Mycobacterium avium subsp. paratuberculosis in sheep. Vaccine 27: 911-918 (2009).

Robinson, M., O’Brien, R., Mackintosh, C. and Griffin, F. Differential immune responses of Red deer (Cervus elaphus) following challenge with Mycobacterium avium subsp. paratuberculosis. Clinical Vaccine Immunology 15: 963-969 (2008).

Mackintosh, C.G., Labes, R.E., Thompson, B.R., Clark, R.G., de Lisle, G.W., Johnstone, P.D., Griffin, J.F.T. Efficacy, immune responses and side-effects of vaccines against Johne's disease in young red deer (Cervus elaphus) experimentally challenged with Mycobacterium avium subsp paratuberculosis. New Zealand Veterinary Journal 56: 1-9 (2008).

Hines M. E. II,. Stabel, J. R., Sweeney, R. W., Griffin, F., Talatt, A. M., Bakker, D., Benedictus, G., Davis, W. C., DeLisle, G. W., Gardner, I.A., Juste, R. A., Kapur, V., Koets, A., McNair, J., Pruitt, G. and Whitlock, R. H. Experimental Challenge Models for Johne’s disease: A Review and proposed International Guidelines. Veterinary Microbiology 122: 197-222 (2007).

Bannantine, J. P., Radosevich, T. J., Stabel, J. R., Berger, S., Griffin, J. F. T. and Paustian, M. L. Production and Characterization of Monoclonal Antibodies against a Major Membrane Protein of Mycobacterium avium subsp. paratuberculosis. Clinical and Vaccine Immunology 14: 312-317 (2007).

Mackintosh, C. G., Labes, R. E., Clark, R. G., deLisle, G. W. and Griffin, J. F. T. Experimental infections in young red deer (Cervus elaphus) with a bovine and ovine strain of Mycobacterium avium subsp. paratuberculosis. New Zealand Verterinary Journal 55: 23-29 (2007).

Berger, S., Bannantine, J. P. and Griffin, J. F. T. Autoreactive antibodies are present in sheep with Johne’s disease and cross-react with Mycobacterium avium subsp. paratuberculosis antigens. Microbes and Infection 9: 963-970 (2007).

Berger, S.T., Hinz, D., Bannantine, J.P. and Griffin, J.F.T. Isolation of High-Affinity Single-Chain Antibodies against Mycobacterium avium subsp.paratuberculosis Surface Proteins from Sheep with Johne’s Disease. Clinical and Vaccine Immunology 13: 1022 – 1029 (2006)

Berger, S.T. and Griffin J.F.T. A Comparison of Ovine monocyte-derived macrophage function following infection with Mycobacterium avium ssp. avium and Mycobacterium avium ssp. paratuberculosis. Immunology and Cell Biology 84: 349 – 356 (2006).

O’Brien, R., Mackintosh, C. G., Bakker, D., Kopecna, M., Pavlik, I., Griffin., J.F.T. Immunological and molecular characterisation of susceptibility in relation to bacterial strain differences in Mycobacterium avium subsp. paratuberculosis infection in red deer (Cervus elaphus). Infection and Immunity. 74: 3530-3537 (2006).

Begg, D., Kemp, R and Griffin, F. Normal levels of immunocompetence in possums (Trichosurus vulpecula) exposed to different laboratory housing conditions post capture immunol Cell Biol.253-256 (2004)

Quershi, T., Labes, R.E., Lambeth, M., Griffin, J.F.T. and Mackintosh, C.G. Transmission of Mycobacterium bovis. From experimentally infected ferrets to non-infected ferrets. NZ Vet. J. 48: 99-104 (2000)

Griffin, J.F.T., Spittle, E., Rodgers, C., Liggett, S., Cooper, M., Bakker, D., Bannantine, J. Immunoglobulin G1 enzyme-linked immunosorbent assay for diagnosis of Johne’s disease in red deer (Cervus elaphus). Clinical & Diagnostic Laboratory Immunology 12: 1401-1409 (2005)

Begg, D., Griffin, J.F.T. Vaccination of sheep against M. Paratuberculosis Immune parameters and protective efficacy. Vaccine. 23: 4999-5008 (2005)

Mackintosh, C.G., Labes, R., Griffin, J.F.T. The effect of Johne’s vaccination on tuberculin testing in farmed red deer (Cervus elaphus) NZVJ. 53: (4) 216-222 (2005)

Begg, D., O’Brien, R., Mackintosh, C.G and Griffin, J.F.T. An experimental infection model for Johne’s disease in sheep. Infect Immun. 73: 5603-5611 (2005)

 

 

 

 

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