Dataset Information

Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine.

ABSTRACT: The presence of galectin-3 was immunohistochemically quantified in bovine intestines infected with paratuberculosis (Johne's disease) to determine whether galectin-3 was involved in the formation of granulation tissue associated with the disease. Mycobacterium avium subsp. paratuberculosis infection was histochemically confirmed using Ziehl-Neelsen staining and molecularly diagnosed through rpoB DNA sequencing. Galectin-3 was detected in the majority of inflammatory cells, possibly macrophages, in the granulomatous lesions within affected tissues, including the ileum. These findings suggest that galectin-3 is associated with the formation of chronic granulation tissues in bovine paratuberculosis, probably through cell adhesion and anti-apoptosis mechanisms.

SUBMITTER: Lee J

PROVIDER: S-EPMC2801129 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine.

Lee Juyeon J Moon Changjong C Kim Jihoon J Jung Chanwoo C Lee Keun-Hwa KH Joo Hong-Gu HG Ahn Meejung M Shin Taekyun T

Journal of veterinary science 20090901 3

The presence of galectin-3 was immunohistochemically quantified in bovine intestines infected with paratuberculosis (Johne's disease) to determine whether galectin-3 was involved in the formation of granulation tissue associated with the disease. Mycobacterium avium subsp. paratuberculosis infection was histochemically confirmed using Ziehl-Neelsen staining and molecularly diagnosed through rpoB DNA sequencing. Galectin-3 was detected in the majority of inflammatory cells, possibly macrophages, ...[more]

PMID: 19687616

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Project description:Various measures have been advocated for the control of Johne's disease (caused by Mycobacterium avium subsp. paratuberculosis, MAP) in different countries. Farmers' compliance has been reported to be variable depending on disease prevalence and incentives to participate in control programs. After the prevalence of MAP shedding and risk factors for within-herd spread of MAP were assessed in 17 Swiss cattle herds (10 dairy and 7 beef), general and herd-specific recommendations were given to the farmers to reduce MAP transmission within the herd. Participation in the study and implementation of control measures were voluntary, no financial incentives were provided for the realization of control measures. After a 3-year period of monitored observation including biannual farm visits and discussion of the situation, the implementation of the recommended control measures and their effect on prevalence of MAP shedding were evaluated. Implementation of recommended general and farm-specific control measures was only partially realized. Neither the number of animals tested positive (before or during the study) nor the farmers' knowledge about paratuberculosis were significantly associated with their compliance for the implementation of management changes. The apparent within-herd prevalence remained constant despite limited implementation of control measures, and no particular group of control measures was found to be associated with changes in prevalence. Farmers' compliance for the implementation of control measures to reduce the impact of Johne's disease in infected farms was very limited under Swiss farming conditions in the frame of voluntary participation in a research project. These results indicate that the losses associated with paratuberculosis in Swiss dairy and beef operations are not estimated to be high enough by the farmers to justify important efforts for control measures, and that incentives may be necessary to achieve efficient implementation of such measures.

Project description:Mycobacterium avium subspecies paratuberculosis (MAP) infection is established following the ingestion of bacteria, their penetration of the intestinal mucosa and subsequent events of the host-parasite interaction. These bacteria invade M cells, macrophages and are capable of resisting host defenses and multiply to reach very high numbers intracellular. Mycobactrium avium subsp. avium (MAA) is an antigenically and genetically similar organisms but is relatively nonpathogenic for cattle. MAA organisms appear to infect cattle, but unlike cattle infected with MAP, cattle infected with MAA typically mount an effective systemic immune response, form caseous granuloma, and eliminate the infection. This study was designed to understand the similarities and differences in the host responses during MAP and MAA infection. Neonatal calves were infected (ligated ileal loops) with PBS, MAP, or avirulent MAA following which samples were collected at 30 min, 1h, 2h, 4h, 8h, or 12h. Post-infection, RNA was collected, processed, and then hybridized to custom bovine gene expression arrays, each of which represented 13,258 transcripts spotted in duplicate. Arrays were normalized by scaling against the average reference intensity value (i.e., average across all arrays), normalized by global mean, and then log transformed before statistical analyses were performed. Pairwise comparisons of averaged signal values and Student’s t test were performed using GeneSifter software (VizX Labs, Seattle, WA). A fold-change of at least 1.5-fold and a p value of 0.05 or less was required for a difference in signal to be considered statistically significant. When comparing the transcriptional responses of calves infected with the MAA versus MAP, unique patterns of expression were clearly visible. In general, numbers of transcripts altered in response to infection were much greater for MAA-infected animals than for those infected with the MAP. No genes were significantly up-regulated in MAP-infected animals at the earliest time point tested (30 min), and only modest numbers of genes were increased in expression over the experimental time course. On the other hand, up-regulated transcripts were detected by 30 min in MAA-infected animals and peaked by 2 hr. Differences in the numbers of down-regulated genes between MAP-infected and MAA-infected animals (compared to PBS-infected controls) were less pronounced. At the earliest time points, MAP-infected calves had a greater number of down-regulated genes than did animals infected with MAA. This trend was reversed at 8 and 12 hr post-infection. Keywords: Gene expression profiling by microarray

Project description:Mycobacterium avium spp. paratuberculosis (MAP) is the causative agent of Johne's disease (JD), also known as paratuberculosis, in ruminants. The mechanisms of JD pathogenesis are not fully understood, but it is known that MAP subverts the host immune system by using macrophages as its primary reservoir. MAP infection in macrophages is often studied in healthy cows or experimentally infected calves, but reports on macrophages from naturally infected cows are lacking. In our study, primary monocyte-derived macrophages (MDMs) from cows diagnosed as positive (+) or negative (-) for JD were challenged in vitro with live MAP. Analysis using next-generation RNA sequencing revealed that macrophages from JD(+) cows did not present a definite pattern of response to MAP infection. Interestingly, a considerable number of genes, up to 1436, were differentially expressed in JD(-) macrophages. The signatures of the infection time course of 1, 4, 8, and 24 h revealed differential expression of ARG2, COL1A1, CCL2, CSF3, IL1A, IL6, IL10, PTGS2, PTX3, SOCS3, TNF, and TNFAIP6 among other genes, with major effects on host signaling pathways. While several immune pathways were affected by MAP, other pathways related to hepatic fibrosis/hepatic stellate cell activation, lipid homeostasis, such as LXR/RXR (liver X receptor/retinoid X receptor) activation pathways, and autoimmune diseases (rheumatoid arthritis or atherosclerosis) also responded to the presence of live MAP. Comparison of the profiles of the unchallenged MDMs from JD(+) vs. JD(-) cows showed that 868 genes were differentially expressed, suggesting that these genes were already affected before monocytes differentiated into macrophages. The downregulated genes predominantly modified the general cell metabolism by downregulating amino acid synthesis and affecting cholesterol biosynthesis and other energy production pathways while introducing a pro-fibrotic pattern associated with foam cells. The upregulated genes indicated that lipid homeostasis was already supporting fat storage in uninfected JD(+) MDMs. For JD(+) MDMs, differential gene expression expounds long-term mechanisms established during disease progression of paratuberculosis. Therefore, MAP could further promote disease persistence by influencing long-term macrophage behavior by using both tolerance and fat-storage states. This report contributes to a better understanding of MAP's controls over the immune cell response and mechanisms of MAP survival.

Dataset Information

Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine.

Publications

Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine.

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