Whole-Blood Gene-Expression Profiles of Cows Infected with Mycobacterium avium subsp. paratuberculosis Reveal Changes in Immune Response and Lipid Metabolism

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic debilitating disease affecting ruminants worldwide. In the present study, we aimed to determine the major gene networks and pathways underlying the immune response to MAP infection using whole-blood cells, as well as provide the potential transcriptional markers for identifying the status of MAP infection. We analyzed the transcriptional profiles of whole-blood cells of cattle identified and grouped according to the presence of MAP-specific antibodies and the MAP shed by them. The grouping was based on the results obtained by ELISA and PCR analyses as follows: i) Test1 group: MAP-negative results obtained by ELISA and positive results obtained by PCR; ii) Test2 group: MAP-positive results obtained by ELISA and negative results obtained by PCR; iii) Test3 group: MAP-positive results obtained by ELISA and positive results obtained by PCR; iv) uninfected control: MAP-negative results obtained both by ELISA and PCR analysis. The results showed down-regulated production and metabolism of reactive oxygen species in the Test1 group, activation of pathways related to the host-defense response against MAP (LXR/RXR activation and complement system) in the Test2 and Test3 groups, and anti-inflammatory response (activation of IL-10 signaling pathway) only in the Test3 group. Our data indicate a balanced response that serves the immune-limiting mechanism while the host-defense responses are progressing.

Gene Expression Profiles of Th1-type Chemokines in Whole Blood of Mycobacterium avium subsp. paratuberculosis-Infected Cattle

“…JD manifests several stages of infection, such as silent, subclinical, clinical, and advanced cell infections, depending on the symptom evaluation and quantification of intestinal MAP (11,12). Additionally, the progression of mycobacterial infection has been thought to be related to Th1 / Th2 migration of the host (13).…”

“…Th1 response decreases as the disease progresses, but the antibody response (Th2 response) to MAP increases (13). Thus, since the Th1 / Th2 shift is related to disease progression and bacterial excretion, many studies have determined the MAP infection stage based on detection of MAP and MAP-specific antibody in specimen such as feces, milk, and sera (12,14,15). DNA-detected with ELISA-negative, and was expected to be detectable at the early state of MAP infection.…”

Establishment a real-time reverse transcription PCR based on host biomarkers for the detection of the subclinical cases of Mycobacterium avium subsp. paratuberculosis

“…Our previous studies also proposed several biomarkers that were up-regulated in MAP infected macrophages, mice, and cattle [21][22][23]. Transcriptional profiles of MAP-infected macrophage RAW 264.7 cells and a mouse model suggested five and three genes as prognostic biomarkers, respectively [21,22]. β-defensins were also suggested as prognostic biomarkers in subclinical animals of MAP-naturally infected cattle [23].…”

“…Moreover, six proteins (transferrin, gelsolin isoforms α & β, complement subcomponent C1r, complement component C3, amine oxidasecopper containing 3, and coagulation factor II) were proposed as biomarkers after they were found to increase by at least 2-fold in MAP-infected cattle, as were two proteins (coagulation factor XIII-B polypeptide, and fibrinogen γ chain and its precursor) that were reduced by nearly two-fold in MAP-infected cattle [20]. Our previous studies also proposed several biomarkers that were up-regulated in MAP infected macrophages, mice, and cattle [21][22][23]. Transcriptional profiles of MAP-infected macrophage RAW 264.7 cells and a mouse model suggested five and three genes as prognostic biomarkers, respectively [21,22].…”

Knowledge gaps that hamper prevention and control ofMycobacterium aviumsubspeciesparatuberculosisinfection

“…Using proteomic and transcriptomic analyses, several putative biomarkers for early infection with MAP have been proposed (Casey et al., ; David, Barkema, Luo Guan, & De Buck, ; David, Barkema, Mortier, et al., ; Seth et al., ; Shin et al., ; Skovgaard et al., ; Thirunavukkarasu et al., ; You et al., ; Zhong, Taylor, Begg, & Whittington, ). Metabolomic profiling detected MAP infection earlier than other diagnostic methods, with individual metabolites distinguishing infected from non‐infected cattle (De Buck, Shaykhutdinov, Barkema, & Vogel, ).…”