<i>Mycobacterium avium</i>subsp<i>. paratuberculosis</i>Infection Causes Suppression of RANTES, Monocyte Chemoattractant Protein 1, and Tumor Necrosis Factor Alpha Expression in Peripheral Blood of Experimentally Infected Cattle

Buza, Joram; Mori, Yoshihide; Bari, Abusaleh Mahfuzul; Aodon-geril, Hirokazu Hikono; Hirayama, Sachiyo; Shu, Yujing; Momotani, Eiichi

doi:10.1128/iai.71.12.7223-7227.2003

Cited by 31 publications

(18 citation statements)

References 21 publications

(25 reference statements)

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“…4C). Cytokine responses observed in the present study were consistent with the findings in previous studies (32,47). Genes associated with a Th1 proinflammatory response (IFN-␥, IL-2, IL-1␤, Il-6, IL-8, IL-17, IL-18, and TNF-␣) and Th17 (IL-17) were upregulated, indicating that at least two T cell subsets were involved in the response to PPDj.…”

Section: Discussionsupporting

confidence: 82%

Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model

Faisal

Chen

Yan

et al. 2013

Clin Vaccine Immunol

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f Johne's disease (JD) is prevalent worldwide and has a significant impact on the global agricultural economy. In the present study, we evaluated the protective efficacy of a leuD (⌬leud) mutant and gained insight into differential immune responses after challenge with virulent M. avium subsp. paratuberculosis in a caprine colonization model. The immune response and protective efficacy were compared with those of the killed vaccine Mycopar. In vitro stimulation of peripheral blood mononuclear cells with johnin purified protein derivative showed that Mycopar and ⌬leuD generated similar levels of gamma interferon (IFN-␥) but significantly higher levels than unvaccinated and challenged phosphate-buffered saline controls. However, only with ⌬leuD was the IFN-␥ response maintained. Flow cytometric analysis showed that the increase in IFN-␥ correlated with proliferation and activation (increased expression of CD25) of CD4, CD8, and ␥␦T cells, but this response was significantly higher in ⌬leuD-vaccinated animals at some time points after challenge. Both Mycopar and ⌬leuD vaccines upregulated Th1/proinflammatory and Th17 cytokines and downregulated Th2/anti-inflammatory and regulatory cytokines at similar levels at almost all time points. However, significantly higher levels of IFN-␥ (at weeks 26 and 30), interleukin-2 (IL-2; week 18), IL-1b (weeks 14 and 22), IL-17 (weeks 18 and 22), and IL-23 (week 18) and a significantly lower level of IL-10 (weeks 14 and 18) and transforming growth factor ␤ (week 18) were detected in the ⌬leuD-vaccinated group. Most importantly, ⌬leuD elicited an immune response that significantly limited colonization of tissues compared to Mycopar upon challenge with wild-type M. avium subsp. paratuberculosis. In conclusion, the ⌬leuD mutant is a promising vaccine candidate for development of a live attenuated vaccine for JD in ruminants.

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Section: Discussionsupporting

confidence: 82%

Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model

Faisal

Chen

Yan

et al. 2013

Clin Vaccine Immunol

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“…Once a high enough intracellular burden has been reached, MAP can trigger necrosis within infected bovine macrophages (Periasamy et al, 2013), suggesting that necrotic macrophages in the early stages of granuloma formation may contribute returning MAP to the host epithelium during the progression of Johne's disease. The model described here, and the inflammatory signals measured during the differing stages of infection, are supported by the scientific literature which has reported the subclinical and clinical stages of Johne's disease and analysed the immunological responses specific to the mucosal intestinal tissue during each stage (Buza et al, 2003;Khare et al, 2012;Lee et al, 2001;Stabel & Robbe-Austerman, 2011;Weiss et al, 2006). Experimental observations support the role of induced immune tolerance in mucosal tissue during early stages of Johne's disease.…”

Section: Discussionsupporting

confidence: 58%

Characterization of the inflammatory phenotype of Mycobacterium avium subspecies paratuberculosis using a novel cell culture passage model

et al. 2015

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Understanding the pathogenic mechanisms of Mycobacterium avium subspecies paratuberculosis (MAP) and the host responses to Johne's disease is complicated by the multi-faceted disease progression, late-onset host reaction and the lack of available ex vivo infection models. We describe a novel cell culture passage model that mimics the course of infection in vivo. The developed model simulates the interaction of MAP with the intestinal epithelial cells, followed by infection of macrophages and return to the intestinal epithelium. MAP internalization triggers a minimal inflammatory response. After passage through a macrophage phase, bacterial reinfection of MDBK epithelial cells, representing the late phase of intestinal mucosal infection, is associated with increased synthesis of the pro-inflammatory transcripts of IL-6, CCL5, IL-8 and IL-18, paired with decreased levels of TGFb. Transcriptome analysis of MAP from each stage of epithelial cell infection identified increased expression of lipid biosynthesis and lipopeptide modification genes in the inflammatory phenotype of MAP. Total lipid analysis by HPLC-ES/MS indicates different lipidomic profiles between the two phenotypes and a unique set of lipids composing the inflammatory MAP phenotype. The presence of selected upregulated lipid-modification gene transcripts in samples of ileal tissue from cows diagnosed with Johne's disease supports and validates the model. By using the relatively simple cell culture passage model, we show that MAP alters its lipid composition during intracellular infection and acquires a pro-inflammatory phenotype, which likely is associated with the inflammatory phase of Johne's disease.

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“…paratuberculosis-infected bovine macrophages (74), the hyporesponsiveness in ileal lymphocytes from Mycobacterium avium subsp. paratuberculosis-infected cows (75), abnormalities in the regulation of cytokine expression (9,13,16,30,31,65,73), the perturbation of macrophage activation and apoptosis (13,15), and the impairment of nitric oxide responsiveness (61 (33,35,68). Local and systemic immune dysfunctions in humans are well-described features of Crohn's disease (39,46).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

Scanu¹,

et al. 2007

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Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P ‫؍‬ 0.0003 for irritable bowel syndrome patients versus healthy controls and P ‫؍‬ 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P ‫؍‬ 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of handmade cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.

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Mycobacterium aviumsubsp. paratuberculosisInfection Causes Suppression of RANTES, Monocyte Chemoattractant Protein 1, and Tumor Necrosis Factor Alpha Expression in Peripheral Blood of Experimentally Infected Cattle

Cited by 31 publications

References 21 publications

Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model

Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model

Characterization of the inflammatory phenotype of Mycobacterium avium subspecies paratuberculosis using a novel cell culture passage model

Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities

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