Specific Antibody and Interferon-Gamma Responses Associated with Immunopathological Forms of Bovine Paratuberculosis in Slaughtered Friesian Cattle

Patricia Vazquez,Ramon A Juste,Joseba M Garrido,Stephen V Gordon

doi:10.1371/journal.pone.0064568

Patricia Vazquez, Ramon A Juste + Show 2 more

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https://doi.org/10.1371/journal.pone.0064568

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Journal: PloS one	Publication Date: May 28, 2013
Citations: 81	License type: CC BY 4.0

Affiliation: Bizkaia Science and Technology Park, Tecnalia

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory regional enteritis in ruminants. Cell-mediated immune responses are assumed to be protective and therefore, to be associated with its more delimited lesion types, while humoral responses are mainly associated with diffuse histopathological lesions. However, this duality of immune responses has been recently questioned. The aim of this study was to assess the relationship between both types of immunological responses and the type and extension of intestinal lesions and the presence of MAP in bovine tissues. Standard histopathological examinations, two microbiological procedures (culture and real time PCR (rtPCR)), as well as MAP specific antibody and interferon gamma (IFN-γ) release assays (IGRA) were performed on tissues and blood of 333 slaughtered Holstein-Friesian animals. Paratuberculous lesions were observed in 176 (52.9%) of the animals and overall MAP detection rates were estimated at 13.5% and 28.5% for tissue culture and rtPCR, respectively. Unlike the relatively constant non-specific IFN-γ release, both the antibody levels and the specific IFN-γ release significantly increased with tissue damage. Delimited immunopathological forms, which accounted for 93.2% of all forms, were mostly related to positive testing in the IGRA (38.4%) whereas diffuse ones (6.8%) were associated with antibody seropositivity (91.7%). However, since the frequency of positive immune responses in both tests increased as the lesions severity increased, polarization of Th1/Th2 responses was less prominent than expected. MAP was detected in the majority of ELISA-positive animals (culture+: 90%, rtPCR+: 85%) but the bacteria was only confirmed in the 36.1% of IGRA-positive animals by any of the two microbiological tests. In terms of diagnosis, the antibody test was a good indicator of advanced tissue damage (diffuse forms), but the IGRA did not associate well with more delimited forms or with MAP detection.

Highlights

Infection with Mycobacterium avium subsp. paratuberculosis (MAP) leads to a slow and progressive granulomatous enteritis and lymphadenitis, known as Paratuberculosis (PTB) or Johne’s disease, affecting domestic and wild ruminant species [1].In dairy cattle, MAP infected cows that present typical clinical symptoms, that is, diarrhea, poor body condition and decreased milk production, are mainly those in their first and second calving
Most of the lesions corresponded to focal forms (86.4%; 152/176) while multifocal and diffuse forms accounted for 13.6% (24/176)
The majority of focal lesions appeared in mesenteric LN (88.8%; 135/152) whereas focal granulomas affecting ileocecal valve (ICV) and distal ileum (DI) accounted for 2.6% (4/152)

Summary

Introduction

Infection with Mycobacterium avium subsp. paratuberculosis (MAP) leads to a slow and progressive granulomatous enteritis and lymphadenitis, known as Paratuberculosis (PTB) or Johne’s disease, affecting domestic and wild ruminant species [1].In dairy cattle, MAP infected cows that present typical clinical symptoms, that is, diarrhea, poor body condition and decreased milk production, are mainly those in their first and second calving. In the initial stages of infection, MAP usually triggers a predominantly pro-inflammatory and cytotoxic cytokine pattern so as to contain the progress of infection [8] This Th1 cell-mediated response is mainly characterized by the release of interferon-gamma (IFN-c), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a) [9,10]. If MAP reactivation occurs or the host immune system is weakened, these proposed resistant forms (focal lesions) can shift to diffuse forms and clinical disease of fatal consequences [14] In these cases, the Th1-type response is overcome by a nonprotective IgG1 mediated response (Th2–type) and the IFN-c levels are reduced mainly because of the effect of two antiinflammatory cytokines: the interleukin-10 (IL-10) and the transforming growth factor beta (TGF-b) [8]. Recent work in ovine PTB, has pointed out that this model might not be so simple and that the immunopathology of PTB needs to be reviewed [15]

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