Experimental infection of lambs with C and S-type strains of Mycobacterium avium subspecies paratuberculosis: immunological and pathological findings

Abstract

The two main genotypes of recognized isolates of Mycobacterium avium subsp. paratuberculosis (Map) are cattle (C) and sheep (S) strains. An experimental infection was conducted to establish the effect of Map strain on the pathogenesis of ovine paratuberculosis. Twenty-four out of thirty 1.5-month-old Assaf lambs were divided into 4 groups of 6 and infected orally with three low passage field isolates, two of S- (22G and the pigmented Ovicap49) and one of C– (764) type, and the reference K-10 strain (C type). The remaining six animals were unchallenged controls. Animals were euthanized at 150 and 390 days post-infection (dpi). Throughout the experiment, the peripheral immune response was assessed and histological and molecular (PCR) studies were conducted on samples of intestine and related lymphoid tissue. Specific antibody and IFN-γ production was significantly higher in animals infected with the C strains, while no consistent IFN- γ responses were observed in the S-type strain infected groups. A positive intradermal skin test response was detected in all infected groups. Lambs infected with S-type strains had granulomatous lesions restricted to the lymphoid tissue with no differences in the lesion intensity over time. In both C–type strain groups, lesions were more severe at 150 dpi while at 390 dpi lesions, characterized by well-demarcated granulomas with fibrosis, decreased in severity. Only infected lambs were positive to PCR. These results suggest that the strain of Map has a strong influence over the immune and pathological responses developed by the host. Lesions induced by C–type strains in lambs show a regressive character and tend to decrease as the infection progresses.

Mycobacterium Avium subsp. Paratuberculosis Isolates Induce In Vitro Granuloma Formation and Show Successful Survival Phenotype, Common Anti-Inflammatory and Antiapoptotic Responses within Ovine Macrophages Regardless of Genotype or Host of Origin

“…We observed that ovine PBMCs infected with Map isolates from sheep and cattle formed well defined aggregates after 10 days of incubation at 37 °C. Map -induced aggregates displayed morphological characteristics similar to natural granulomas, such as three-dimensional aggregation of lymphocytes around macrophages In accordance with our results, granulomatous lesions consistent with Map infection have been recently found in tissue sections from lambs experimentally infected with bovine (C-type) and ovine (S-type) isolates of Map [42]. The advantages of in vitro models of granuloma include reduced cost, increased control, and that they can provide insights into host-mycobacteria interactions at stages of granuloma formation too early to address with animal models.…”

Macrophage Subsets Within Granulomatous Intestinal Lesions in Bovine Paratuberculosis

“…They were unvaccinated Holstein cows coming from 2 different herds in whom a follow-up study on losses due to paratuberculosis was ongoing. Infection was confirmed by bacteriological culture of frozen tissues, 18 serum indirect enzyme-linked immunosorbent assay, 14 …”

“…However, in some cases, this polarization of forms is not so clearly defined. 14,56,58 Map infection occurs mainly through M cells of the Peyer's patches and, to a lesser extent, through differentiated epithelial cells. 49 After penetrating the intestinal epithelial barrier, Map invades the subepithelial macrophages that play a crucial role in the host-pathogen interaction.…”

“…,36 and IFN-g release test,14,36 following the methodology detailed in the referred articles. Complete information on the animals and the results of the different tests are provided inSupplemental Table 1.…”

Detection of Mycobacterium avium subsp. paratuberculosis in reproductive tissue and semen of naturally infected rams

“…This had an effect on the results, since not all the rams were positive to the localization tests and the identification of MAP in the intestine (ileum). This is possibly due to the type of MAP strain, since it has been reported that the lambs infected with Type C strains presented a higher inflammatory response, while in those infected with the Type S strain, the lesions were minimal (Fernández et al, 2014).…”