- Personal Center
- Logout
FOLLOWUS
- Current Issue
- Current Issue
- Latest Articles
- Archive
- Special Issues
Effects of
Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes- Military Medical Research Vol. 7, Issue 2, Pages: 125-139(2020)
- Affiliations：
Army Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, the 8th Medical Center of Chinese PLA General Hospital, Beijing 100091, China
- Author bio：
* xueqiongwu@139.com
- Funds：
DOI：10.1186/s40779-020-00258-4
CLC：-
Published：2020-06
- Accepted：
Scan QR Code
Cite this article as: Gong et al.: Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes. Mil Med Res, 2020, 7: 25
Cite this article as: Gong et al.: Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes. Mil Med Res, 2020, 7: 25 DOI： 10.1186/s40779-020-00258-4.
摘要
Abstract
Background:
2
Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine
but not widely used in many parts of the world due to a variety of issues.
Mycobacterium vaccae
(
M. vaccae
) is another vaccine used in human subjects to prevent tuberculosis. In the current study
we investigated the potential mechanisms of
M. vaccae
vaccination by determining differentially expressed genes in mice infected with
M. tuberculosis
before and after
M. vaccae
vaccination.
Methods:
2
Three days after exposure to
M. tuberculosis
H37Rv strain (5×10
5
CFU)
adult BALB/c mice randomly received either
M. vaccae
vaccine (22.5 μg) or vehicle
via
intramuscular injection (
n
=8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.
Results:
2
M. vaccae
vaccination provided protection against
M. tuberculosis
infection (most prominent in the lungs). We identified 2
326 upregulated and 2
221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional.
Conclusions:
2
M. vaccae
vaccine provided good protection in mice against
M. tuberculosis
infection
via
a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.
关键词
Keywords
references
Gordon SV , Parish T . Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe . Microbiology (Reading, Engl). 2018 ; 164 ( 4 ): 437 – 9 .
Gong W , Liang Y , Wu X . The current status, challenges, and future developments of new tuberculosis vaccines[J] . Hum Vaccin Immunother. 2018 ; 14 ( 7 ): 1697 – 716 .
Colditz GA , Brewer TF , Berkey CS , Wilson ME , Burdick E , Fineberg HV , et al . Efficacy of BCG vaccine in the prevention of tuberculosis . Meta-analysis of the published literature. JAMA. 1994 ; 271 ( 9 ): 698 – 702 .
Fine PE . Variation in protection by BCG: implications of and for heterologous immunity . Lancet. 1995 ; 346 ( 8986 ): 1339 – 45 .
Huang CY , Hsieh WY . Efficacy of Mycobacterium vaccae immunotherapy for patients with tuberculosis: a systematic review and meta-analysis . Hum Vaccin Immunother. 2017 ; 13 ( 9 ): 1960 – 71 .
WHO . Global tuberculosis report 2017 . Geneva : World Health Organization ; 2017 . Report No.: 978–92–4-156551-6 Contract No.: 20 .
Tsukamura M , Mizuno S , Tsukamura S . Classification of rapidly growing mycobacteria . Jpn J Microbiol. 1968 ; 12 ( 2 ): 151 – 66 .
Rodriguez-Guell E , Agusti G , Corominas M , Cardona PJ , Luquin M , Julian E . Mice with pulmonary tuberculosis treated with Mycobacterium vaccae develop strikingly enhanced recall gamma interferon responses to M. vaccae cell wall skeleton . Clin Vaccine Immunol. 2008 ; 15 ( 5 ): 893 – 6 .
Skinner MA , Yuan S , Prestidge R , Chuk D , Watson JD , Tan PL . Immunization with heat-killed Mycobacterium vaccae stimulates CD8 + cytotoxic T cells specific for macrophages infected with Mycobacterium tuberculosis[J] . Infect Immun. 1997 ; 65 ( 11 ): 4525 – 30 .
Hernandez-Pando R , Aguilar D , Orozco H , Cortez Y , Brunet LR , Rook GA . Orally administered Mycobacterium vaccae modulates expression of immunoregulatory molecules in BALB/c mice with pulmonary tuberculosis . Clin Vaccine Immunol. 2008 ; 15 ( 11 ): 1730 – 6 .
Zhang L , Jiang Y , Cui Z , Yang W , Yue L , Ma Y , et al . Mycobacterium vaccae induces a strong Th1 response that subsequently declines in C57BL/6 mice[J] . J Vet Sci. 2016 ; 17 ( 4 ): 505 – 13 .
Stanford JL , Bahr GM , Rook GA , Shaaban MA , Chugh TD , Gabriel M , et al . Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis . Tubercle. 1990 ; 71 ( 2 ): 87 – 93 .
Weng H , Huang JY , Meng XY , Li S , Zhang GQ . Adjunctive therapy of Mycobacterium vaccae vaccine in the treatment of multidrug-resistant tuberculosis: a systematic review and meta-analysis . Biomed Rep. 2016 ; 4 ( 5 ): 595 – 600 .
Yang XY , Chen QF , Li YP , Wu SM . Mycobacterium vaccae as adjuvant therapy to anti-tuberculosis chemotherapy in never-treated tuberculosis patients: a meta-analysis . PLoS One. 2011 ; 6 ( 9 ): e23826 .
Luo Y , Lu S , Guo S . Immunotherapeutic effect of Mycobacterium vaccae on multi-drug resistant pulmonary tuberculosis . Zhonghua Jie He He Hu Xi Za Zhi. 2000 ; 23 ( 2 ): 85 – 88 . [Article in China] .
Fonken LK , Frank MG , D'Angelo HM , Heinze JD , Watkins LR , Lowry CA , et al . Mycobacterium vaccae immunization protects aged rats from surgeryelicited neuroinflammation and cognitive dysfunction . Neurobiol Aging. 2018 ; 71 : 105 – 14 .
Cananzi FC , Mudan S , Dunne M , Belonwu N , Dalgleish AG . Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma . Hum Vaccin Immunother. 2013 ; 9 ( 11 ): 2427 – 33 .
Frank MG , Fonken LK , Dolzani SD , Annis JL , Siebler PH , Schmidt D , et al . Immunization with Mycobacterium vaccae induces an anti-inflammatory milieu in the CNS: attenuation of stress-induced microglial priming, alarmins and anxiety-like behavior . Brain Behav Immun. 2018 ; 73 : 352 – 63 .
Zheng J , Chen L , Liu L , Li H , Liu B , Zheng D , et al . Proteogenomic analysis and discovery of immune antigens in Mycobacterium vaccae . Mol Cell Proteomics. 2017 ; 16 ( 9 ): 1578 – 90 .
Li C , Jiang X , Luo M , Feng G , Sun Q , Chen Y . Mycobacterium vaccae nebulization can protect against asthma in BALB/c mice by regulating Th9 expression[J] . PLoS One. 2016 ; 11 ( 8 ): e0161164 .
Fowler DW , Copier J , Wilson N , Dalgleish AG , Bodman-Smith MD . Mycobacteria activate gammadelta T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy . Cancer Immunol Immunother. 2012 ; 61 ( 4 ): 535 – 47 .
Liang Y , Zhang J , Yang Y , Bai X , Yu Q , Li N , et al . Immunogenicity and therapeutic effects of recombinant Ag85AB fusion protein vaccines in mice infected with Mycobacterium tuberculosis . Vaccine. 2017 ; 35 ( 32 ): 3995 – 4001 .
Liang Y , Zhang X , Bai X , Xiao L , Wang X , Zhang J , et al . Immunogenicity and therapeutic effects of a Mycobacterium tuberculosis rv2190c DNA vaccine in mice . BMC Immunol. 2017 ; 18 ( 1 ): 11 .
Gong W , Xiong X , Qi Y , Jiao J , Duan C , Wen B . Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice . Vaccine. 2014 ; 32 ( 18 ): 2027 – 33 .
Gong WP , Wang PC , Xiong XL , Jiao J , Yang XM , Wen BH . Chloroformmethanol residue of Coxiella burnetii markedly potentiated the specific Immunoprotection elicited by a recombinant protein fragment rOmpB-4 derived from outer membrane protein B of rickettsia rickettsii in C3H/HeN mice . PLoS One. 2015 ; 10 ( 4 ): e0124664 .
Gong WP , Wang PC , Xiong XL , Jiao J , Yang XM , Wen BH . Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by immunization with a combination of a recombinant adhesin rAdr2 and a protein fragment rOmpB-4 derived from outer membrane protein B . Vaccine. 2015 ; 33 ( 8 ): 985 – 92 .
Gong W , Qi Y , Xiong X , Jiao J , Duan C , Wen B . Rickettsia rickettsii outer membrane protein YbgF induces protective immunity in C3H/HeN mice . Hum Vaccin Immunother. 2015 ; 11 ( 3 ): 642 – 9 .
Wang PC , Xiong XL , Jiao J , Yang XM , Jiang YQ , Wen BH , et al . Th1 epitope peptides induce protective immunity against rickettsia rickettsii infection in C3H/HeN mice . Vaccine. 2017 ; 35 ( 51 ): 7204 – 12 .
Xu LJ , Wang YY , Zheng XD , Gui XD , Tao LF , Wei HM . Immunotherapeutical potential of Mycobacterium vaccae on M. tuberculosis infection in mice . Cell Mol Immunol. 2009 ; 6 ( 1 ): 67 – 72 .
Groschel MI , Prabowo SA , Cardona PJ , Stanford JL , van der Werf TS . Therapeutic vaccines for tuberculosis--a systematic review . Vaccine. 2014 ; 32 ( 26 ): 3162 – 8 .
Rodriguez-Guell E , Agusti G , Corominas M , Cardona PJ , Casals I , Parella T , et al . The production of a new extracellular putative long-chain saturated polyester by smooth variants of Mycobacterium vaccae interferes with Th1-cytokine production . Antonie Van Leeuwenhoek. 2006 ; 90 ( 1 ): 93 – 108 .
Gerstmayer B , Kusters D , Gebel S , Muller T , Van Miert E , Hofmann K , et al . Identification of RELMgamma, a novel resistin-like molecule with a distinct expression pattern . Genomics. 2003 ; 81 ( 6 ): 588 – 95 .
Koizumi G , Kumai T , Egawa S , Yatomi K , Hayashi T , Oda G , et al . Gene expression in the vascular wall of the aortic arch in spontaneously hypertensive hyperlipidemic model rats using DNA microarray analysis . Life Sci. 2013 ; 93 ( 15 ): 495 – 502 .
Schinke T , Haberland M , Jamshidi A , Nollau P , Rueger JM , Amling M . Cloning and functional characterization of resistin-like molecule gamma . Biochem Biophys Res Commun. 2004 ; 314 ( 2 ): 356 – 62 .
Gleeson LE , Sheedy FJ , Palsson-McDermott EM , Triglia D , O'Leary SM , O'Sullivan MP , et al . Cutting edge: Mycobacterium tuberculosis induces aerobic glycolysis in human alveolar macrophages that is required for control of intracellular bacillary replication . J Immunol. 2016 ; 196 ( 6 ): 2444 – 9 .
Sambarey A , Devaprasad A , Baloni P , Mishra M , Mohan A , Tyagi P , et al . Meta-analysis of host response networks identifies a common core in tuberculosis . NPJ Syst Biol Appl. 2017 ; 3 : 4 .
Boro M , Balaji KN . CXCL1 and CXCL2 regulate NLRP3 Inflammasome activation via G-protein-coupled receptor CXCR2 . J Immunol. 2017 ; 199 ( 5 ): 1660 – 71 .
Yu EA , John SH , Tablante EC , King CA , Kenneth J , Russell DG , et al . Host transcriptional responses following ex vivo re-challenge with Mycobacterium tuberculosis vary with disease status . PLoS One. 2017 ; 12 ( 10 ): e0185640 .
Nishimura J , Saiga H , Sato S , Okuyama M , Kayama H , Kuwata H , et al . Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor . J Immunol. 2008 ; 180 ( 6 ): 4032 – 9 .
Tateosian NL , Pasquinelli V , Hernandez Del Pino RE , Ambrosi N , Guerrieri D , Pedraza-Sanchez S , et al . The impact of IFN-gamma receptor on SLPI expression in active tuberculosis: association with disease severity . Am J Pathol. 2014 ; 184 ( 5 ): 1268 – 73 .
Gomez SA , Arguelles CL , Guerrieri D , Tateosian NL , Amiano NO , Slimovich R , et al . Secretory leukocyte protease inhibitor: a secreted pattern recognition receptor for mycobacteria . Am J Respir Crit Care Med. 2009 ; 179 ( 3 ): 247 – 53 .
Gopal R , Monin L , Torres D , Slight S , Mehra S , McKenna KC , et al . S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis . Am J Respir Crit Care Med. 2013 ; 188 ( 9 ): 1137 – 46 .
Mirzaei A , Mahmoudi H . Evaluation of TNF-alpha cytokine production in patients with tuberculosis compared to healthy people . GMS Hyg Infect Control. 2018 ; 13 : Doc09 .
Oh JH , Yang CS , Noh YK , Kweon YM , Jung SS , Son JW , et al . Polymorphisms of interleukin-10 and tumour necrosis factor-alpha genes are associated with newly diagnosed and recurrent pulmonary tuberculosis . Respirology. 2007 ; 12 ( 4 ): 594 – 8 .
Basingnaa A , Antwi-Baffour S , Nkansah DO , Afutu E , Owusu E . Plasma levels of cytokines (IL-10, IFN-γ and TNF-α) in multidrug resistant tuberculosis and drug responsive tuberculosis patients in Ghana . Diseases. 2018 ; 7 ( 1 ). pii: E2 . doi: 10.3390/diseases7010002 http://doi.org/10.3390/diseases7010002 doi: 10.3390/diseases7010002.
Wang Y , Zhou X , Lin J , Yin F , Xu L , Huang Y , et al . Effects of Mycobacterium bovis on monocyte-derived macrophages from bovine tuberculosis infection and healthy cattle . FEMS Microbiol Lett. 2011 ; 321 ( 1 ): 30 – 6 .
Meng W , Bai B , Bai Z , Li Y , Yue P , Li X , et al . The immunosuppression role of alpha-fetoprotein in human hepatocellular carcinoma . Discov Med. 2016 ; 21 ( 118 ): 489 – 94 .
Corapcioglu F , Guvenc BH , Sarper N , Aydogan A , Akansel G , Arisoy ES . Peritoneal tuberculosis with elevated serum CA 125 level mimicking advanced ovarian carcinoma in an adolescent . Turk J Pediatr. 2006 ; 48 ( 1 ): 69 – 72 .
Limaiem F , Gargouri F , Bouraoui S , Lahmar A , Mzabi S . Co-existence of hepatocellular carcinoma and hepatic tuberculosis . Surg Infect. 2014 ; 15 ( 4 ): 437 – 40 .
Champion TC , Partridge LJ , Ong SM , Malleret B , Wong SC , Monk PN . Monocyte subsets have distinct patterns of tetraspanin expression and different capacities to form multinucleate giant cells . Front Immunol. 2018 ; 9 : 1247 .
Bermudez LE , Goodman J . Mycobacterium tuberculosis invades and replicates within type II alveolar cells . Infect Immun. 1996 ; 64 ( 4 ): 1400 – 6 .
Bermudez LE , Sangari FJ , Kolonoski P , Petrofsky M , Goodman J . The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells . Infect Immun. 2002 ; 70 ( 1 ): 140 – 6 .
Hall-Stoodley L , Watts G , Crowther JE , Balagopal A , Torrelles JB , Robison-Cox J , et al . Mycobacterium tuberculosis binding to human surfactant proteins a and D, fibronectin, and small airway epithelial cells under shear conditions . Infect Immun. 2006 ; 74 ( 6 ): 3587 – 96 .
Fortune SM , Solache A , Jaeger A , Hill PJ , Belisle JT , Bloom BR , et al . Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms . J Immunol. 2004 ; 172 ( 10 ): 6272 – 80 .
Doz E , Rose S , Court N , Front S , Vasseur V , Charron S , et al . Mycobacterial phosphatidylinositol mannosides negatively regulate host toll-like receptor 4, MyD88-dependent proinflammatory cytokines, and TRIF-dependent costimulatory molecule expression . J Biol Chem. 2009 ; 284 ( 35 ): 23187 – 96 .
Giacomini E , Iona E , Ferroni L , Miettinen M , Fattorini L , Orefici G , et al . Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response . J Immunol. 2001 ; 166 ( 12 ): 7033 – 41 .
Sugawara I , Yamada H , Mizuno S , Takeda K , Akira S . Mycobacterial infection in MyD88-deficient mice . Microbiol Immunol. 2003 ; 47 ( 11 ): 841 – 7 .
Wright KM , Friedland JS . Regulation of monocyte chemokine and MMP-9 secretion by proinflammatory cytokines in tuberculous osteomyelitis . J Leukoc Biol. 2004 ; 75 ( 6 ): 1086 – 92 .
Gu X , Gao Y , Mu DG , Fu EQ . MiR-23a-5p modulates mycobacterial survival and autophagy during Mycobacterium tuberculosis infection through TLR2/MyD88/NF-kappaB pathway by targeting TLR2 . Exp Cell Res. 2017 ; 354 ( 2 ): 71 – 7 .
Chen CS , Alonso JL , Ostuni E , Whitesides GM , Ingber DE . Cell shape provides global control of focal adhesion assembly . Biochem Biophys Res Commun. 2003 ; 307 ( 2 ): 355 – 61 .
Theocharis AD , Skandalis SS , Gialeli C , Karamanos NK . Extracellular matrix structure . Adv Drug Deliv Rev. 2016 ; 97 : 4 – 27 .
Bonnans C , Chou J , Werb Z . Remodelling the extracellular matrix in development and disease . Nat Rev Mol Cell Biol. 2014 ; 15 ( 12 ): 786 – 801 .
Del Angel-Mosqueda C , Gutierrez-Puente Y , Lopez-Lozano AP , Romero-Zavaleta RE , Mendiola-Jimenez A , Medina-De la Garza CE , et al . Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro . Head Face Med. 2015 ; 11 : 29 .
Villasenor T , Madrid-Paulino E , Maldonado-Bravo R , Urban-Aragon A , Perez-Martinez L , Pedraza-Alva G . Activation of the Wnt pathway by Mycobacterium tuberculosis: a Wnt-Wnt situation . Front Immunol. 2017 ; 8 : 50 .
Zhang X , Huang T , Wu Y , Peng W , Xie H , Pan M , et al . Inhibition of the PI3KAkt-mTOR signaling pathway in T lymphocytes in patients with active tuberculosis . Int J Infect Dis. 2017 ; 59 : 110 – 7 .
0
Views
0
Downloads
0
CSCD
- L-PDFDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19
京公网安备11010802024621 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.