Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model
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Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of the disease. Therefore, an in vivo murine experimental model was tried to understand responses in early stage of MAP infection by oral and intraperitoneal (IP) routes. In the MAP infection size, and weight of spleen and liver were increased in the IP group compared with oral groups. Severe histopathological changes were also observed in the spleen and liver of IP infected mice at 12 weeks post-infection (PI). Acid-fast bacterial burden in the organs was closely related to histopathological lesions. In the cytokine production from splenocytes of MAP-infected mice, higher amounts of in TNF-α, IL-10, and IFN-γ were produced at early stage of IP-infected mice while IL-17 production was different at time and infected groups. This phenomenon may indicate the immune shift from Th1 to Th17 through the time course of MAP infection. Systemic and local responses in the MAP-infection were analyzed by using transcriptomic analysis in the spleens and mesenteric lymph nodes (MLN). Based on the analysis of biological processes at 6 weeks PI in spleen and MLN in each infection group, canonical pathways were analyzed with ingenuity pathway analysis in the immune responses and metabolism especially lipid metabolism. Infected host cells with MAP increased in the production of proinflammatory cytokines and reduced the availability of glucose at early stage of infection ( p < 0.05). Also, host cells secreted cholesterol through cholesterol efflux to disturb energy source of MAP. These results reveal immunopathological and metabolic responses in the early stage of MAP infection through the development of a murine model.Keywords:
Mesenteric lymph nodes
Splenocyte
Proinflammatory cytokine
Pathogenesis
Johne's disease (JD) is a chronic and progressive intestinal disease in ruminants caused by Mycobacterium avium subspecies paratuberculosis (Map). The usual route of infection is fecal-oral. The disease manifests in adult cows and results in economic losses. Although Map does not propagate in the environment, it survives for long periods in different environmental conditions expected on many dairy farms. Johne's disease control programs have been developed in different countries and in several US states with a goal to test and classify herds of cattle as infected or presumptively noninfected with maximum accuracy and least cost. Generally, these programs utilize recognized laboratory tests such as ELISA or direct microbiological individual fecal culture. However, these tests have several disadvantages, especially when applied in herds with subclinical disease or low prevalence. Since Map is shed into the environment by dairy cattle through fecal contamination and appears to survive well, a better understanding of Map distribution in the environment could lead to improved herd-screening alternatives.
Objectives of the study were: 1) to describe Map distribution and prevalence in the environment on Minnesota dairy farms, and 2) to assess the relationship between culture status of Map in the farm environment and fecal-pooled culture status on dairy farms.
Subclinical infection
Cattle Diseases
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Johne's disease (JD) is a chronic debilitating intestinal disease of ruminants, caused by the infectious agent Mycobacterium avium subspecies paratuberculosis (MAP). JD is widely disseminated in dairy farms and known to cause considerable economic loss. Recently, interest in the detection of clinical and subclinical manifestations of the disease and MAP has created interest in developing cost efficient methods for its detection. The culture of soil samples contaminated with MAP (called environmental samples) offers an economic, easily performed, detection technique on dairy farms. The objective of this investigation was to conduct environmental testing on two dairies (E and W; n=>2500) in Texas known to have clinical cases of JD and previous isolations of MAP from fecal cultures.
Subclinical infection
Subspecies
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Johne's disease (paratuberculosis) control programs involve both herd management changes to limit transmission of Mycobacterium avium subspecies paratuberculosis infections to calves, as well as testing of adult cattle to detect those that serve as the source of infection. No work has yet been reported on economic optimization, i.e., cost-benefit analysis, of paratuberculosis control programs.
Disease Control
Dairy industry
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Pasteurization
Forbearance
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The ability of Mycobacterium avium subsp. paratuberculosis to survive in bovine monocytes was studied using radiometric (BACTEC) culture, standard plate counting and microscopic counting of acid-fast stained monocyte monolayers. Results of microscopic counts sharply contrasted with results of viable counts determined both by plate counting and radiometric counting. We observed an early phase (the first 6 d after in vitro infection) of intracellular bacillary growth, followed by a later phase of mycobacteriostasis or killing (up to 12 d after in vitro infection) in monocytes from non-infected cows. The data suggest that multiplication and death of M. avium subsp. paratuberculosis occur simultaneously in bovine monocytes infected in vitro. Using the BACTEC method, we compared the ability of bovine monocytes from normal cows and cows infected with M. avium subsp. paratuberculosis and showing evidence of a strong Thl-like cellular immune response to ingest and inhibit the intracellular growth of M. avium subsp. paratuberculosis. There was a trend toward greater phagocytosis and faster killing of Mycobacterium avium subsp. paratuberculosis by monocytes from the infected, immune responder cows. However, the observed numbers of viable M. avium subsp. paratuberculosis at each time after monocyte infection were not significantly different between normal and infected cows.
Monocyte
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Johne's Disease (JD) is an important infectious disease of cattle caused by Mycobacterium avium subspecies paratuberculosis (MAP). It is estimated that over 50% of US dairy herds are infected with MAP. Current JD diagnostic tests detect either an immune response to MAP or the actual organism in feces or tissues. The JD ELISA detects antibodies to MAP and is the most common assay used to detect an MAP immune response. Because of the pathogenesis of JD, the sensitivity of the JD ELISA is reported to be less than 50% when used to detect JD infected adult cattle. The specificity of the JD ELISA is reported to be greater than 90%. However, the assay specificity may vary significantly between herds. In this case study, low MAP ELISA specificity in an individual dairy herd is described.
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Mycobacterium avium subspecies paratuberculosis is the causative agent of paratuberculosis in cattle which causes a chronic infection of the small intestine. Since the transmission is only partly understood current control programs have been able to only decrease prevalence but not to eradicate disease from a herd. Unknown and therefore uncontrolled routes of transmission were suggested and infective bioaerosols were hypothesized as a potential candidate. This review gives an overview concerning disease transmission and focuses on consequences of bioaerosols on the within-herd transmission of paratuberculosis.
Indoor bioaerosol
Disease Control
Disease Transmission
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Caprine paratuberculosis is a mycobacterial, chronic, debilitating, progressive, granulomatous, intestinal infectious disease of goats. The aim of this study was to detect Mycobacterium avium subspecies paratuberculosis (MAP) in blood and fecal samples of goats. Blood and fecal samples were collected from goats (n=200). Acid fast staining was done in fecal samples. The IS900 PCR assay targeting MAP with amplicons of 413bp from both blood and fecal samples and TaqMan real time PCR to further confirm the disease was performed. Nine (4.5%) animals were positive for M. avium subspecies paratuberculosis by conventional PCR. Out of these 9 animals, four were positive for MAP in both fecal and blood samples. However by TaqMan real time PCR, thirteen (6.5%) animals were positive for MAP. Thus the present study reports the prevalence of caprine paratuberculosis in Punjab.
TaqMan
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