Cellular and Cytokine Responses in the Granulomas of Asymptomatic Cattle naturally infected with Mycobacterium bovis in Ethiopia

ABSTRACTCellular (CD3+ T cell and CD68+ macrophages), cytokines (IFN-γ+ and TNF-α+) and effector molecule (iNOS+) responses were evaluated in the lymph nodes and tissue of cattle naturally infected with Mycobacterium bovis. Detailed post mortem and immunonohistochemical examinations of lesions were performed on 16 cows positive for single intradermal cervical comparative tuberculin test (SICCTT) and identified from dairy farms located around the Addis Ababa City. The severity of the gross lesion was significantly higher (p=0.003) in M. bovis culture positive (n=12) cows than in culture negative (n=4). Immunohistochemical techniques showed that the mean percentage labelling of CD3+ T cells decreased as the stage of granuloma increased from stage I to stage IV in culture positive cows (p<0.001). On the other hand, the proportional fraction of CD68+ macrophages and the concentrations of IFN-γ+, TNF-α+ and iNOS+ increased significantly from stage I to stage IV (p< 0.001) in culture positive cows. At the early stage of the granuloma, the culture negative cows showed significantly higher mean proportions of CD68+ macrophages (p=0.03) as well as the concentrations of iNOS+ (p=0.007) compared to culture positive cows. Similarly, at advanced granuloma stages, culture negative cows demonstrated significantly higher mean proportions of CD3+ T cells (p< 0.001) compared to culture positive cows. Thus, the present study demonstrated that following natural infection of cows with M. bovis, as the stage of granuloma increases from stage I to stage IV, the proportion of CD3+ cells decreases while the immunolabeling fraction of CD68+ macrophages, IFN-γ+, TNF-α and iNOS+ increases.

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Cellular and Cytokine Responses in the Granulomas of Asymptomatic Cattle Naturally Infected with Mycobacterium bovis in Ethiopia

Infection and Immunity ◽

10.1128/iai.00507-20 ◽

2020 ◽

Vol 88 (12) ◽

Author(s):

Begna Tulu ◽

Henny M. Martineau ◽

Aboma Zewude ◽

Fekadu Desta ◽

David A. Jolliffe ◽

...

Keyword(s):

T Cells ◽

Mycobacterium Bovis ◽

Natural Infection ◽

Stage Iv ◽

Stage I ◽

Content Type ◽

Tnf Α ◽

Ifn Γ ◽

Culture Positive ◽

Culture Negative

ABSTRACT Cell (CD3+ T cell and CD68+ macrophages), cytokine (interferon gamma-positive [IFN-γ+] and tumor necrosis factor alpha-positive [TNF-α+]), and effector molecule (inducible nitric oxide synthase-positive [iNOS+]) responses were evaluated in the lymph nodes and tissues of cattle naturally infected with Mycobacterium bovis. Detailed postmortem and immunohistochemical examinations of lesions were performed on 16 cows that were positive by the single intradermal cervical comparative tuberculin (SICCT) test and that were identified from dairy farms located around the city of Addis Ababa, Ethiopia. The severity of the gross lesion was significantly higher (P = 0.003) in M. bovis culture-positive cows (n = 12) than in culture-negative cows (n = 4). Immunohistochemical techniques showed that in culture-positive cows, the mean immunolabeling fraction of CD3+ T cells decreased as the stage of granuloma increased from stage I to stage IV (P < 0.001). In contrast, the CD68+ macrophage, IFN-γ+, TNF-α+, and iNOS+ immunolabeling fractions increased from stage I to stage IV (P < 0.001). In the early stages, culture-negative cows showed a significantly higher fraction of CD68+ macrophage (P = 0.03) and iNOS+ (P = 0.007) immunolabeling fractions than culture-positive cows. Similarly, at advanced granuloma stages, culture-negative cows demonstrated significantly higher mean proportions of CD3+ T cells (P < 0.001) than culture-positive cows. Thus, this study demonstrates that, following natural infection of cows with M. bovis, as the stage of granuloma increases from stage I to stage IV, the immunolabeling fraction of CD3+ cells decreases, while the CD68+ macrophage, IFN-γ+, TNF-α+, and iNOS+ immunolabeling fractions increases.

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Elevated levels of proinflammatory and anti-inflammatory cytokines in patients with bladder cancer depending on a tumor stage

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2020.8632 ◽

2020 ◽

Vol 93 (1) ◽

Author(s):

Viktor Dmytryk ◽

Tetiana Luhovska ◽

Pavel Yakovlev ◽

Olexiy Savchuk ◽

Ludmila Ostapchenko ◽

...

Keyword(s):

Bladder Cancer ◽

Stage Iv ◽

Tumor Stage ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Common Disease ◽

Tnf Α ◽

Ifn Γ ◽

Th 1

Bladder Cancer (BC) is a common disease worldwide. Chronic inflammation is one of the key mechanisms for the development of BC. This study enrolled 40 patients. Preoperative plasma levels of IL-1β, IL-4, IL-6, IL-10, IL-12β, TNF-α and IFN-γ were determined by ELISA. In our study, we observed diverse changes in the levels of cytokines in patients with BC Stage I, II, III and IV. The levels of IL-1β was increased for stage I, stage II, and stage III. The level of TNF-α was increased for stage II, stage III, stage IV. The levels of IL-4, IL-6, IL-10 and IL-12β were increased in patients with stage III and IV only. The levels of IFN- γ declined for stage II, stage III and stage IV with the lowest levels in patients with Stage IV. In our study, we investigated alteration in levels of Th-1 and Th-2-like cytokine profile, but some deficiency in Th1- status discovered in patients with BC.

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Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or Regulatory T Cell Responses in Adults

Clinical and Vaccine Immunology ◽

10.1128/cvi.00162-15 ◽

2015 ◽

Vol 22 (7) ◽

pp. 778-788 ◽

Cited By ~ 31

Author(s):

Mardi C. Boer ◽

Corine Prins ◽

Krista E. van Meijgaarden ◽

Jaap T. van Dissel ◽

Tom H. M. Ottenhoff ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mycobacterium Bovis ◽

Regulatory T Cell ◽

Cell Response ◽

T Cell Response ◽

Bcg Vaccination ◽

Cell Responses ◽

Tnf Α ◽

Ifn Γ

ABSTRACTMycobacterium bovisbacillus Calmette-Guérin (BCG), the only currently available vaccine against tuberculosis, induces variable protection in adults. Immune correlates of protection are lacking, and analyses on cytokine-producing T cell subsets in protected versus unprotected cohorts have yielded inconsistent results. We studied the primary T cell response, both proinflammatory and regulatory T cell responses, induced by BCG vaccination in adults. Twelve healthy adult volunteers who were tuberculin skin test (TST) negative, QuantiFERON test (QFT) negative, and BCG naive were vaccinated with BCG and followed up prospectively. BCG vaccination induced an unexpectedly dichotomous immune response in this small, BCG-naive, young-adult cohort: BCG vaccination induced either gamma interferon-positive (IFN-γ+) interleukin 2-positive (IL-2+) tumor necrosis factor α-positive (TNF-α+) polyfunctional CD4+T cells concurrent with CD4+IL-17A+and CD8+IFN-γ+T cells or, in contrast, virtually absent cytokine responses with induction of CD8+regulatory T cells. Significant induction of polyfunctional CD4+IFN-γ+IL-2+TNF-α+T cells and IFN-γ production by peripheral blood mononuclear cells (PBMCs) was confined to individuals with strong immunization-induced local skin inflammation and increased serum C-reactive protein (CRP). Conversely, in individuals with mild inflammation, regulatory-like CD8+T cells were uniquely induced. Thus, BCG vaccination either induced a broad proinflammatory T cell response with local inflammatory reactogenicity or, in contrast, a predominant CD8+regulatory T cell response with mild local inflammation, poor cytokine induction, and absent polyfunctional CD4+T cells. Further detailed fine mapping of the heterogeneous host response to BCG vaccination using classical and nonclassical immune markers will enhance our understanding of the mechanisms and determinants that underlie the induction of apparently opposite immune responses and how these impact the ability of BCG to induce protective immunity to TB.

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Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis

Infection and Immunity ◽

10.1128/iai.00704-09 ◽

2009 ◽

Vol 77 (11) ◽

pp. 4837-4846 ◽

Cited By ~ 18

Author(s):

Ajay Grover ◽

Jennifer Taylor ◽

JoLynn Troudt ◽

Andrew Keyser ◽

Kimberly Arnett ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Mycobacterium Bovis ◽

T Cell Activation ◽

Guinea Pigs ◽

Cell Activation ◽

Activated T Cells ◽

Bcg Vaccination ◽

Tnf Α ◽

Ifn Γ

ABSTRACT The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-γ) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+ CD62Llow and CD8+ CD62Llow) and mRNA expression of IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-γ mRNA expression but decreased TNF-α mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-γ mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+ CD62Llow T cells at day 40, although the numbers of CD8+ CD62Llow T cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection.

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Differentiation between Mycobacterium bovis BCG-Vaccinated and M. bovis-Infected Cattle by Using Recombinant Mycobacterial Antigens

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.1.1-5.1999 ◽

1999 ◽

Vol 6 (1) ◽

pp. 1-5 ◽

Cited By ~ 96

Author(s):

Bryce M. Buddle ◽

Natalie A. Parlane ◽

Denise L. Keen ◽

Frank E. Aldwell ◽

John M. Pollock ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Bovine Tuberculosis ◽

Secreted Proteins ◽

Infected Cattle ◽

Recombinant Antigens ◽

Purified Protein Derivative ◽

Ifn Γ ◽

Mycobacterial Antigens ◽

Culture Positive ◽

Culture Negative

ABSTRACT Tuberculosis continues to be a worldwide problem for both humans and animals. The development of tests to differentiate between infection with Mycobacterium tuberculosis orMycobacterium bovis and vaccination with M. bovis BCG could greatly assist in the diagnosis of early infection as well as enhance the use of tuberculosis vaccines on a wider scale. Recombinant forms of four major secreted proteins ofM. bovis—MPB59, MPB64, MPB70, and ESAT-6—were tested in a whole-blood gamma interferon (IFN-γ) assay for differentiation between cattle vaccinated with BCG and those experimentally infected with M. bovis. BCG vaccination induced minimal protection in the present study, with similar numbers of animals infected withM. bovis in BCG-vaccinated and nonvaccinated groups. Following vaccination with BCG, the animals produced moderate IFN-γ responses to bovine purified protein derivative (PPDB) but very weak responses to the recombinant antigens. Cattle from both the BCG-vaccinated and nonvaccinated groups which were M. bovisculture positive following challenge produced IFN-γ responses to PPDB and ESAT-6 which were significantly stronger than those observed in the corresponding M. bovis culture-negative animals. IFN-γ responses to MPB59, MPB64, and MPB70 were significantly weaker, and these antigens could not discriminate between vaccinated animals which develop disease and the culture-negative animals. The results of the study indicate that of the four antigens tested in the IFN-γ assay, only ESAT-6 would be suitable for differentiating BCG-vaccinated animals from those infected with bovine tuberculosis.

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