Impact of Mycobacterium avium subsp. paratuberculosis infection on bovine IL10RA knockout mammary epithelial (MAC-T) cells

Shandilya, Umesh K.; Wu, Xiang; McAllister, Caitlin; Mutharia, Lucy M.; Karrow, Niel A.

doi:10.1007/s11626-023-00758-2

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…In the comparison of WT versus WT-MAP, we identified DE genes involved in the immune system, including transcription factor Jun ( Jun ), which was downregulated in WT-MAP. The Jun pathway has been implicated in the activation of transcription of IL10 in T helper 2 cells, which are a major source of IL10 [ 39 ], and MAC-T cells are also capable of producing IL10 [ 40 ]. Another identified DE gene was interleukin 6 ( IL6 ), which was upregulated in WT-MAP.…”

Section: Discussionmentioning

confidence: 99%

“…All the experiments were carried out in quadruplicate at four independent times. Bacteria was cultured using the methods described by Shandilya et al [ 40 ], and the bacterial load was added to each infected treatment group to form a 10:1 multiplicity of infection [ 40 , 64 ]. There were four treatment groups, described in Table 1 , with unedited and IL10Rα knockout cells infected with MAP bacteria or not.…”

Section: Methodsmentioning

confidence: 99%

“…There were four treatment groups, described in Table 1 , with unedited and IL10Rα knockout cells infected with MAP bacteria or not. As described in Shandilya et al [ 40 ], MAC-T cells had MAP bacteria added (for 72 h), or for uninfected cells, MAP carrier solution media was added. Extraction of mRNA was performed using the same method as Shandilya et al [ 65 ] using the RNeasy Mini Kit (Quiagen, Germany).…”

Section: Methodsmentioning

confidence: 99%

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The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

Fong,

Rochus,

Shandilya

et al. 2024

BMC Genom Data

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Background Johne’s disease is a chronic wasting disease caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Johne’s disease is highly contagious and MAP infection in dairy cattle can eventually lead to death. With no available treatment for Johne’s disease, genetic selection and improvements in management practices could help reduce its prevalence. In a previous study, the gene coding interleukin-10 receptor subunit alpha (IL10Rα) was associated with Johne’s disease in dairy cattle. Our objective was to determine how IL10Rα affects the pathogenesis of MAP by examining the effect of a live MAP challenge on a mammary epithelial cell line (MAC-T) that had IL10Rα knocked out using CRISPR/cas9. The wild type and the IL10Rα knockout MAC-T cell lines were exposed to live MAP bacteria for 72 h. Thereafter, mRNA was extracted from infected and uninfected cells. Differentially expressed genes were compared between the wild type and the IL10Rα knockout cell lines. Gene ontology was performed based on the differentially expressed genes to determine which biological pathways were involved. Results Immune system processes pathways were targeted to determine the effect of IL10Rα on the response to MAP infection. There was a difference in immune response between the wild type and IL10Rα knockout MAC-T cell lines, and less difference in immune response between infected and not infected IL10Rα knockout MAC-T cells, indicating IL10Rα plays an important role in the progression of MAP infection. Additionally, these comparisons allowed us to identify other genes involved in inflammation-mediated chemokine and cytokine signalling, interleukin signalling and toll-like receptor pathways. Conclusions Identifying differentially expressed genes in wild type and ILR10α knockout MAC-T cells infected with live MAP bacteria provided further evidence that IL10Rα contributes to mounting an immune response to MAP infection and allowed us to identify additional potential candidate genes involved in this process. We found there was a complex immune response during MAP infection that is controlled by many genes.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

Fong,

Rochus,

Shandilya

et al. 2024

BMC Genom Data

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“…This model was also used to evaluate the co-infection processes of MAP and other pathogens, such as Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae, and demonstrated the rapid baso-apical translocation of MAP in epithelial cells [187], and the fast internalization of S. aureus in MAC-T cells previously infected by MAP [188]. The knockout variants of TLR 4 or IL-10Rα of this model have recently been used to demonstrate the role of those receptors in the regulation of the innate response to MAP [189,190].…”

Section: Epithelial Cell Linesmentioning

confidence: 99%

Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies

Jolly,

Fernández,

Mundo

et al. 2023

Animals

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Paratuberculosis is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. Paratuberculosis that affects a wide variety of domestic and wild animals. It is considered one of the diseases with the highest economic impact on the ruminant industry. Despite many efforts and intensive research, paratuberculosis control still remains controversial, and the existing diagnostic and immunoprophylactic tools have great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Ruminant animal models can be restricted by several reasons, related to space requirements, the cost of the animals, and the maintenance of the facilities. Therefore, we review the potential and limitations of the different experimental approaches currently used in paratuberculosis research, focusing on laboratory animals and cell-based models. The aim of this review is to offer a vision of the models that have been used, and what has been achieved or discovered with each one, so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

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“…The mRNA expression profile of bovine macrophage responses during inflammation from MAP infection has been described [ 20 , 21 ]. Genetic variations in several candidate genes expressed in macrophages were associated with resistance/susceptibility to MAP infection, including NOD2 [ 22 ], IL10 [ 23 , 24 , 25 ], SLC11A1, and Toll-like receptor genes [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of Transcriptome Profiles and lncRNA–miRNA–mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne’s Disease in Dairy Cattle

Ghafouri,

Dehghanian Reyhan,

Sadeghi

et al. 2024

ncRNA

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Paratuberculosis or Johne’s disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.

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Impact of Mycobacterium avium subsp. paratuberculosis infection on bovine IL10RA knockout mammary epithelial (MAC-T) cells

Cited by 5 publications

References 51 publications

The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies

Integrated Analysis of Transcriptome Profiles and lncRNA–miRNA–mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne’s Disease in Dairy Cattle

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