Immunogenicity of mycobacterial PPE44 (Rv2770c) in Mycobacterium bovis BCG-infected mice

2005 ◽  
Vol 54 (5) ◽  
pp. 443-448 ◽  
Author(s):  
Daniela Bonanni ◽  
Laura Rindi ◽  
Nicoletta Lari ◽  
Carlo Garzelli
Keyword(s):  
Mycobacterium Bovis ◽  
Delayed Type Hypersensitivity ◽  
Mycobacterial Antigen ◽  
Moderate Degree ◽  
Bacille Calmette Guerin ◽  
Infection Models ◽  
Ifn Γ ◽  
Low Levels ◽  
Draining Lymph Nodes ◽  
Igg1 Isotype

The Pro-Pro-Glu (PPE) protein family of Mycobacterium tuberculosis includes 69 glycine-rich proteins with a conserved N-terminal domain. Their role in tuberculosis is unknown, but it has been speculated that they may have an important immunological significance. In this investigation, the immunogenicity of the ppe44 (Rv2770c) gene product in BALB/c mice infected subcutaneously or intravenously with Mycobacterium bovis bacille Calmette–Guérin (BCG) was evaluated. Mice infected subcutaneously developed high titres of anti-PPE44 IgG1 antibodies, while PPE44-specific IgG2a antibodies were absent at all times tested. PPE44-primed cells from draining lymph nodes and spleen produced low levels of IFN-γ, and a moderate degree of delayed-type hypersensitivity was observed following PPE44 intracutaneous challenge. In mice infected intravenously, the anti-PPE44 IgG1 antibody response was markedly higher compared with the subcutaneous infection; anti-PPE44 IgG2a antibodies at titres approximately 0.5–2.0 log10 lower than IgG1 were detected. Interferon (IFN)-γ production in PPE44-stimulated spleen-cell cultures was transient. These results indicate that PPE44 represents a novel mycobacterial antigen expressed during subcutaneous and intravenous infection by M. bovis BCG in BALB/c mice. Both infection models seem to polarize the immune response to PPE44 towards a Th2 phenotype, as testified by the IgG1 isotype being predominant over IgG2a and by the low IFN-γ and delayed-type hypersensitivity responses.

scholarly journals Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens

2021 ◽  
Vol 8 ◽  
Author(s):  
Heike Köhler ◽  
Elisabeth Liebler-Tenorio ◽  
Valerie Hughes ◽  
Karen Stevenson ◽  
Douwe Bakker ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Mycobacterium Bovis ◽  
Mycobacterium Avium ◽  
Large Individual ◽  
Mycobacterial Antigen ◽  
Protein Antigens ◽  
Recombinant Peptide ◽  
Crude Antigen ◽  
Diagnostic Potential ◽  
Ifn Γ

Despite its potential for early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) infection, the IFN-γ release assay is not used routinely, because of low specificity of the established crude antigen preparation Johnin (PPDj). Limited data are available assessing the potential of MAP-derived protein and lipopeptide antigens to replace PPDj in assays for goats, while cattle and sheep have been studied more extensively. Furthermore, MAP infection is claimed to interfere with the diagnosis of bovine tuberculosis when other crude antigen preparations (PPDb, PPDa) are applied. In this study, the diagnostic potential of MAP-derived recombinant protein antigens, synthetic MAP lipopentapeptides and of Mycobacterium bovis-specific peptide cocktails was assessed compared to crude mycobacterial antigen preparations in experimentally infected goats. Goats were inoculated with MAP, or Mycobacterium avium subsp. hominissuis (MAH) as surrogate for environmental mycobacteria, non-exposed animals served as controls. Mycobacterium avium Complex-specific antibody and PPDj-induced IFN-γ responses were monitored in vivo. Infection status was assessed by pathomorphological findings and bacteriological tissue culture at necropsy 1 year after inoculation. The IFN-γ response to 13 recombinant protein antigens of MAP, two synthetic MAP lipopentapeptides and three recombinant peptide cocktails of Mycobacterium bovis was investigated at three defined time points after infection. At necropsy, MAP or MAH infection was confirmed in all inoculated goats, no signs of infection were found in the controls. Antibody formation was first detected 3–6 weeks post infection (wpi) in MAH-inoculated and 11–14 wpi in the MAP-inoculated goats. Maximum PPDj-induced IFN-γ levels in MAH and MAP exposed animals were recorded 3–6 and 23–26 wpi, respectively. Positive responses continued with large individual variation. Antigens Map 0210c, Map 1693c, Map 2020, Map 3651cT(it), and Map 3651c stimulated increased whole blood IFN-γ levels in several MAP-inoculated goats compared to MAH inoculated and control animals. These IFN-γ levels correlated with the intensity of the PPDj-induced responses. The two synthetic lipopentapeptides and the other MAP-derived protein antigens had no discriminatory potential. Stimulation with Mycobacterium bovis peptide cocktails ESAT6-CFP10, Rv3020c, and Rv3615c did not elicit IFN-γ production. Further work is required to investigate if test sensitivity will increase when mixtures of the MAP-derived protein antigens are applied.

scholarly journals Priming by DNA Immunization Augments Protective Efficacy of Mycobacterium bovis Bacille Calmette-Guerin against Tuberculosis

2001 ◽  
Vol 69 (6) ◽  
pp. 4174-4176 ◽  
Author(s):  
Carl G. Feng ◽  
Umaimainthan Palendira ◽  
Caroline Demangel ◽  
Joanne M. Spratt ◽  
Adam S. Malin ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Protective Efficacy ◽  
Mycobacterial Antigen ◽  
Dna Immunization ◽  
Bacille Calmette Guerin

ABSTRACT Sequential immunization with mycobacterial antigen Ag85B-expressing DNA and Mycobacterium bovis bacille Calmette-Guerin (BCG) was more effective than BCG immunization in protecting againstMycobacterium tuberculosis infection. Depletion of the CD8+ T cells in the immunized mice impaired protection in their spleens, indicating that this improved efficacy was partially mediated by CD8+ T cells.

Frequency of IFN-γ producing cells correlates with adjuvant enhancement of bacille Calmette-Guèrin induced protection against Mycobacterium bovis

Vaccine ◽  
2005 ◽  
Vol 23 (48-49) ◽  
pp. 5526-5532 ◽  
Author(s):  
Karen E. Logan ◽  
Mark A. Chambers ◽  
R. Glyn Hewinson ◽  
Philip J. Hogarth
Keyword(s):  
Mycobacterium Bovis ◽  
Bacille Calmette Guerin ◽  
Ifn Γ

scholarly journals Identification of N6,N6-Dimethyladenosine in Transfer RNA from Mycobacterium bovis Bacille Calmette-Guérin

Molecules ◽  
2011 ◽  
Vol 16 (6) ◽  
pp. 5168-5181 ◽  
Author(s):  
Clement Chan ◽  
Yok Hian Chionh ◽  
Chia-Hua Ho ◽  
Kok Seong Lim ◽  
I. Ramesh Babu ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Transfer Rna ◽  
Bacille Calmette Guerin

scholarly journals Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

2006 ◽  
Vol 75 (3) ◽  
pp. 1154-1166 ◽  
Author(s):  
Laura H. Hogan ◽  
Dominic O. Co ◽  
Jozsef Karman ◽  
Erika Heninger ◽  
M. Suresh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bacterial Load ◽  
Granulomatous Inflammation ◽  
Cd8 T Cell ◽  
Activated T Cells ◽  
Immunodeficient Mice ◽  
Ifn Γ

ABSTRACT The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.

100 years of Mycobacterium bovis bacille Calmette-Guérin

2021 ◽  
Author(s):  
Christoph Lange ◽  
Peter Aaby ◽  
Marcel A Behr ◽  
Peter R Donald ◽  
Stefan H E Kaufmann ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Bacille Calmette Guerin

scholarly journals Immune Responses to Defined Antigens of Mycobacterium bovis in Cattle Experimentally Infected with Mycobacterium kansasii

2006 ◽  
Vol 13 (6) ◽  
pp. 611-619 ◽  
Author(s):  
W. R. Waters ◽  
M. V. Palmer ◽  
T. C. Thacker ◽  
J. B. Payeur ◽  
N. B. Harris ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Bovine Tuberculosis ◽  
Nontuberculous Mycobacteria ◽  
Gamma Interferon ◽  
Delayed Type Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
Specific Serum ◽  
Specific Proteins

ABSTRACT Cross-reactive responses elicited by exposure to nontuberculous mycobacteria often confound the interpretation of antemortem tests for Mycobacterium bovis infection of cattle. The use of specific proteins (e.g., ESAT-6, CFP-10, and MPB83), however, generally enhances the specificity of bovine tuberculosis tests. While genes for these proteins are absent from many nontuberculous mycobacteria, they are present in M. kansasii. Instillation of M. kansasii into the tonsillar crypts of calves elicited delayed-type hypersensitivity and in vitro gamma interferon and nitrite concentration responses of leukocytes to M. avium and M. bovis purified protein derivatives (PPDs). While the responses of M. kansasii-inoculated calves to M. avium and M. bovis PPDs were approximately equivalent, the responses of M. bovis-inoculated calves to M. bovis PPD exceeded their respective responses to M. avium PPD. The gamma interferon and nitrite responses of M. kansasii-inoculated calves to recombinant ESAT-6-CFP-10 (rESAT-6-CFP-10) exceeded corresponding responses of noninoculated calves as early as 15 and 30 days after inoculation, respectively, and persisted throughout the study. The gamma interferon and nitrite responses of M. bovis-inoculated calves to rESAT-6-CFP-10 exceeded the corresponding responses of M. kansasii-inoculated calves beginning 30 days after inoculation. By using a lipoarabinomannan-based enzyme-linked immunosorbent assay, specific serum antibodies were detected as early as 50 days after challenge with M. kansasii. By a multiantigen print immunoassay and immunoblotting, serum antibodies to MPB83, but not ESAT-6 or CFP-10, were detected in M. kansasii-inoculated calves; however, responses to MPB83 were notably weaker than those elicited by M. bovis infection. These findings indicate that M. kansasii infection of calves elicits specific responses that may confound the interpretation of bovine tuberculosis tests.

scholarly journals Prior Exposure to Live Mycobacterium bovis BCG Decreases Cryptococcus neoformans-Induced Lung Eosinophilia in a Gamma Interferon-Dependent Manner

2003 ◽  
Vol 71 (6) ◽  
pp. 3384-3391 ◽  
Author(s):  
Gerhard Walzl ◽  
Ian R. Humphreys ◽  
Ben G. Marshall ◽  
Lorna Edwards ◽  
Peter J. M. Openshaw ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Mycobacterium Bovis ◽  
Mycobacterial Infection ◽  
Gamma Interferon ◽  
Delayed Type Hypersensitivity ◽  
Infection Model ◽  
Dependent Manner ◽  
Interleukin 5 ◽  
Lung Eosinophilia ◽  
Mycobacterial Antigens

ABSTRACT Some common childhood infections appear to prevent the development of atopy and asthma. In some Mycobacterium bovis BCG-vaccinated populations, strong delayed-type hypersensitivity responses to mycobacterial antigens are associated with a reduced risk of atopy. Although BCG exposure decreases allergen-induced lung eosinophilia in animal models, little attention has been given to the effect of immunity to BCG on responses against live pathogens. We used the murine Cryptococcus neoformans infection model to investigate whether prior BCG infection can alter such responses. The present study shows that persistent pulmonary BCG infection of C57BL/6 mice induced an increase in gamma interferon, a reduction in interleukin-5, and a decrease in lung eosinophilia during subsequent Cryptococcus infection. This effect was long lasting, depended on the presence of live bacteria, and required persistence of mycobacterial infection in the lung. Reduction of eosinophilia was less prominent after infection with a mutant BCG strain (ΔhspR), which was rapidly cleared from the lungs. These observations have important implications for the development of vaccines designed to prevent Th2-mediated disease and indicate that prior lung BCG vaccination can alter the pattern of subsequent host inflammation.

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