scholarly journals Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG)

Vaccine ◽  
2014 ◽  
Vol 32 (45) ◽  
pp. 5998-6004 ◽  
Author(s):  
Richard Copin ◽  
Mireia Coscollá ◽  
Efstratios Efstathiadis ◽  
Sebastien Gagneux ◽  
Joel D. Ernst
Keyword(s):  
Mycobacterium Bovis ◽  
Bacillus Calmette Guerin ◽  
In Vitro Evolution ◽  
Antigenic Diversity

scholarly journals Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection

2020 ◽  
Author(s):  
Jinrui Xu ◽  
Yanbing Zhou ◽  
Yi Yang ◽  
Cuiping Lv ◽  
Xiaoming Liu ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Abc Transporters ◽  
Alveolar Macrophages ◽  
Cholesterol Metabolism ◽  
Present Report ◽  
Host Cells ◽  
Bacillus Calmette Guerin ◽  
Public Health Burden ◽  
Intracellular Cholesterol

Abstract Background: Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis ( M. tuberculosis , Mtb ) i nfection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis Bacillus Calmette–Guérin (BCG). Methods: In the present report, the involvements of ABC-transporters and ACAT1-mediated intracellular cholesterol in autophagy of bovine alveolar macrophages induced by Mycobacterium bovis BCG were interrogated by enzymatic and biochemistry assays in vitro, including quantitative RT-PCR and immunoblotting assays. Results: The results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection. Conclusion: This study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections .

scholarly journals Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Vectors Prime for Strong Cellular Responses to Simian Immunodeficiency Virus Gag in Rhesus Macaques

2014 ◽  
Vol 21 (10) ◽  
pp. 1385-1395 ◽  
Author(s):  
Jaimie D. Sixsmith ◽  
Michael W. Panas ◽  
Sunhee Lee ◽  
Geoffrey O. Gillard ◽  
KeriAnn White ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Mycobacterium Bovis ◽  
Rhesus Macaques ◽  
Vaccine Vector ◽  
Effective Vaccine ◽  
Bacillus Calmette Guerin ◽  
Immunodeficiency Virus ◽  
Specific Priming

ABSTRACTLive attenuated nonpathogenicMycobacterium bovisbacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gagexpression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in anin vitroscreen for augmented immunogenicity. We demonstrated that BCG-SIVgagis able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.

scholarly journals Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection

2020 ◽  
Author(s):  
Jinrui Xu ◽  
Yanbing Zhou ◽  
Yi Yang ◽  
Cuiping Lv ◽  
Xiaoming Liu ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Abc Transporters ◽  
Alveolar Macrophages ◽  
Cholesterol Metabolism ◽  
Present Report ◽  
Host Cells ◽  
Bacillus Calmette Guerin ◽  
Public Health Burden ◽  
Intracellular Cholesterol

Abstract Background: Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis ( M. tuberculosis , Mtb ) i nfection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis Bacillus Calmette–Guérin (BCG). Methods: In the present report, the involvements of ABC-transporters and ACAT1-mediated intracellular cholesterol in autophagy of bovine alveolar macrophages induced by Mycobacterium bovis BCG were interrogated by enzymatic and biochemistry assays in vitro, including quantitative RT-PCR and immunoblotting assays. Results: The results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection. Conclusion: This study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections .

Formation of Multinucleated Giant Cells (MGC) in Vitro by Sensitized Macrophages Exposed to Mycobacterium Bovis

1976 ◽  
Vol 34 ◽  
pp. 224-225
Author(s):  
Alwin H. Warfel ◽  
John Hadden ◽  
Nina Lampen ◽  
Dolores Pla ◽  
Etienne de Harven
Keyword(s):  
Mycobacterium Bovis ◽  
Polymorphonuclear Leukocytes ◽  
Mononuclear Cells ◽  
Central Area ◽  
Giant Cells ◽  
Plastic Substrate ◽  
In Vitro Cultivation ◽  
Bacillus Calmette Guerin ◽  
Multinucleated Giant Cells

Adult rabbits were injected intravenously with heat killed Mycobacterium bovis strain Bacillus Calmette-Guerin (BCG) suspended in oil. As reported previously (1) the rabbits develop a strong infiltration of mononuclear cells which can easily be demonstrated in the lungs 40-50 days post-sensitization. Cells lavaged from these lungs consists of about 82% macrophages, 14% lymphocytes, 3% polymorphonuclear leukocytes and 1% giant cells. Within five to six hours after in vitro cultivation with heat-killed BCG, the macrophages which have already attached to the plastic substrate form clusters apparently by migration. When the mixed population of lavaged cells is cultured for 24 hours many macrophages seem to fuse to form multinucleated giant cells (MGC), whereas cells collected from unsensitized rabbits do not form significant numbers of MGC. A typical MGC containing at least 35 nuclei in the central area of the syncytium is shown in Fig. 1. The mechanism involved in this cell fusion process is not understood.

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