Innate immune markers that distinguish red deer (Cervus elaphus) selected for resistant or susceptible genotypes for Johne's disease

Abstract

While many factors contribute to resistance and susceptibility to infectious disease, a major component is the genotype of the host and the way in which it is expressed. Johne’s disease is a chronic inflammatory bowel disease affecting ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). We have previously identified red deer breeds (Cervus elaphus) that are resistant; have a low rate of MAP infection and do not progress to develop Johne’s disease. In contrast, susceptible breeds have a high rate of MAP infection as seen by seroconversion and progress to develop clinical Johne’s disease. The aim of this study was to determine if immunological differences exist between animals of resistant or susceptible breeds. Macrophage cultures were derived from the monocytes of deer genotypically defined as resistant or susceptible to the development of Johne’s disease. Following in vitro infection of the cells with MAP, the expression of candidate genes was assessed by quantitative PCR as well as infection rate and cell death rate. The results indicate that macrophages from susceptible animals show a significantly higher upregulation of inflammatory genes (iNOS, IL-1α, TNF-α and IL-23p19) than the macrophages from resistant animals. Cells from resistant animals had a higher rate of apoptosis at 24 hours post infection (hpi) compared to macrophages from susceptible animals. The excessive expression of inflammatory mRNA transcripts in susceptible animals could cause inefficient clearing of the mycobacterial organism and the establishment of disease. Controlled upregulation of inflammatory pathways coupled with programmed cell death in the macrophages of resistant animals may predispose the host to a protective immune response against this mycobacterial pathogen.

Evaluation of age-dependent susceptibility in calves infected with two doses of Mycobacterium avium subspecies paratuberculosis using pathology and tissue culture

“…Consequently, marker-assisted breeding might be implemented in JD prevention and control strategies [ 38 ]. Genetic susceptibility traits have also been found in deer; some breeds of red deer vary in resistance/susceptibility [ 39 ]. Based on these previous findings, we speculated that the genetic variation related to the regulation of the cellular immune response could be responsible for observed differences in host responses.…”

Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data

“…However, this will require sampling of macrophages from the site of infection, which is not practical. Since JD-status(resistance)-dependent difference of macrophage phenotype (cytokine expression and apoptosis) was reported in macrophages derived from circulating monocytes, it would be of interest to examine if such ante-mortem macrophage assay has a value in diagnosis of JD status 56 or test for exosomes in serum that are secreted by infected macrophages.…”

Knowledge gaps that hamper prevention and control ofMycobacterium aviumsubspeciesparatuberculosisinfection

“…Genetics as an approach to disease control is an emerging discipline. Identifying the genetic basis of the lower susceptibility will provide possibilities for selection for resistance to MAP infection in dairy and beef cattle, as has been done with Red deer (Dobson, Liggett, O'Brien, & Griffin, ). While genetic improvement for disease resistance is slow, the results are permanent (van Hulzen et al., ; Kirkpatrick & Shook, ).…”