Upregulation of transforming growth factor-beta and interleukin-10 in cows with clinical Johne’s disease

Khalifeh, Mohammad; Stabel, J. R.

doi:10.1016/j.vetimm.2004.01.009

Cited by 66 publications

(64 citation statements)

References 20 publications

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“…paratuberculosis infection than in clinically infected cows (13). Conversely, IL-10 and TGF-␤ gene expression was upregulated in cows with clinical disease.…”

Section: Discussionmentioning

confidence: 85%

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Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival ofMycobacterium aviumsubsp.paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle

Khalifeh

Stabel

2004

Infect Immun

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Gamma interferon (IFN-␥) plays a significant role in the control of mycobacterial infections, includingMycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor ␤ (TGF-␤), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-␥, IL-10, and TGF-␤ by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-␥, IL-10, and TGF-␤ on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-␤ in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-␤, but after stimulation with live M. avium subsp. paratuberculosis, TGF-␤ levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-␤ to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-␤ during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

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“…paratuberculosis infection than in clinically infected cows (13). Conversely, IL-10 and TGF-␤ gene expression was upregulated in cows with clinical disease.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, we found that the immunomodulatory cytokines TGF-␤ and IL-10 were upregulated in the tissues of cows with clinical Johne's disease (13). The presence of anti-inflammatory cytokines that modulate the effects of proinflammatory cytokines, such as IFN-␥, might be one mechanism that enhances the survival of mycobacteria within the host.…”

mentioning

confidence: 99%

Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival ofMycobacterium aviumsubsp.paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle

Khalifeh

Stabel

2004

Infect Immun

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“…25 A reciprocal relationship has been documented between the host T-cell responses and the extent of disease during mycobacterial infections. 12,14,29 Studies of human patients infected with M. tuberculosis suggest a predominance of Th1-mediated immunity in the early stages of disease, with a shift to Th2-mediated immunity in the more advanced stages. 5 This shift in host immunity has also been observed for cows infected with M. paratuberculosis, with strong IFN-c responses noted in the early stages of disease, followed by an upregulation of IL-10 in the latter stages.…”

Section: Introductionmentioning

confidence: 99%

“…5 This shift in host immunity has also been observed for cows infected with M. paratuberculosis, with strong IFN-c responses noted in the early stages of disease, followed by an upregulation of IL-10 in the latter stages. 14,27 Although secretion of other Th1-driven cytokines has been studied, the enhanced expression and secretion of IFN-c in the early stages of infection suggests that this cytokine is critical for controlling mycobacterial infections. The upregulation of IFN-c also makes it an attractive tool for the detection of subclinical infection in cattle with paratuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Augmentation of Secreted and Intracellular Gamma Interferon following Johnin Purified Protein Derivative Sensitization of Cows Naturally Infected withMycobacterium AviumSubsp.Paratuberculosis

Stabel

Kimura²,

Robbe‐Austerman

2007

J VET Diagn Invest

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Abstract. Measurement of secreted interferon (IFN)-c has proven to be a valuable tool for the detection of animals infected with mycobacterial pathogens, including Mycobacterium avium subsp. paratuberculosis. Previous reports have suggested that tuberculin skin testing can influence the performance of the IFN-c assay. In the present study, healthy noninfected cows, and cows subclinically and clinically infected with M. paratuberculosis were administered an intradermal injection of johnin purified protein derivative (JPPD) and effects on secreted and intracellular IFN-c were observed. Intradermal injection resulted in significant increases in secreted IFN-c for subclinically infected cows after stimulation of peripheral blood mononuclear cells (PBMC) with concanavalin A or M. paratuberculosis antigen preparations (whole-cell sonicate and JPPD) on days 7 and 10 postinjection. Intracellular IFN-c was increased after intradermal injection in total PBMC for all treatment groups and was higher within CD4+ and CD8+ subpopulations for infected cows compared to healthy controls throughout the study. When T-cell populations were further defined by CD45RO expression, intracellular IFN-c was higher within CD8+/CD45RO+ lymphocytes compared to CD4+/CD45RO+ cells for subclinically and clinically infected cows but similar within these subpopulations for healthy controls. These results indicate that intradermal sensitization of cows in the subclinical stage of infection will upregulate expression of IFN-c, enhancing the sensitivity of this assay. In addition, CD8+ lymphocytes appear to play an important role as a mediator of M. paratuberculosis infection in naturally exposed cattle.

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“…As infection progresses to a clinical state, bacterial shedding in feces and serum antibody titers increase while IFN-γ production declines. Cows with clinical paratuberculosis showed increased IL-10 and TGF-β cytokine gene expression in ileo compared with subclinically infected animals, which may be indicative of mechanisms causing a shift in T helper (Th) responses from Th1 toward Th2 type [22].…”

Section: Introductionmentioning

confidence: 99%

Bovine IgG1 antibodies againstMycobacterium aviumsubsp.paratuberculosisprotein p34-cx improve association of bacteria and macrophages

et al. 2007

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-Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (Map), is a chronic granulomatous enteric disease in cattle. Among molecular components of Map, protein p34 was identified as specific and immunodominant for bovine B cells. In order to determine if specific antibodies could influence the course of Map pathogenesis, the interaction between bacteria and bovine macrophages was studied. Bovine polyclonal antibodies from 3 calves vaccinated with protein p34-cx, 6 calves vaccinated with heatkilled Map, 8 naturally infected, and 3 healthy calves -as negative controls-were used. Specific anti-Map, -p34-cx and -PPA-3 antibodies were evaluated and isotype characterized. Infected and Map vaccinated animals showed similar IgG1 and IgG2 response against Map whole bacteria. When p34-cx was used as the antigen, mainly IgG1 and IgG3 were detected in infected and only IgG1 in p34-cx vaccinated animals. Bovine polyclonal antibodies from three animals of each category were isolated and affinity purified through Map and p34-cx columns. The effect of these antibodies in association with Map and a transformed bovine peritoneal macrophage's cell line (Bov-Mac) as well as activation of NF-κB transcription factor was studied. Our results show that association of Map significantly increased in vitro after pretreatment with bovine anti-Map or anti-p34-cx antibodies obtained from vaccinated or infected cattle when compared with those of controls. Improved activation of NF-κB was detected in macrophages that ingested Map opsonized with either anti-Map or anti-p34-cx specific antibodies of infected or vaccinated calves, suggesting that both anti-Map and IgG1 anti-p34-cx antibodies support Map-macrophage interactions.Mycobacterium avium subsp. paratuberculosis / p34 / IgG1 / macrophages / cattle

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Upregulation of transforming growth factor-beta and interleukin-10 in cows with clinical Johne’s disease

Cited by 66 publications

References 20 publications

Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival ofMycobacterium aviumsubsp.paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle

Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival ofMycobacterium aviumsubsp.paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle

Augmentation of Secreted and Intracellular Gamma Interferon following Johnin Purified Protein Derivative Sensitization of Cows Naturally Infected withMycobacterium AviumSubsp.Paratuberculosis

Bovine IgG1 antibodies againstMycobacterium aviumsubsp.paratuberculosisprotein p34-cx improve association of bacteria and macrophages

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