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Mycobacterium marinum: a potential immunotherapy for Mycobacterium tuberculosis infection.

Tian WW, Wang QQ, Liu WD, Shen JP, Wang HS - Drug Des Devel Ther (2013)

Bottom Line: Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively).The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1β, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively).In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, People's Republic of China.

ABSTRACT

Purpose: The aim of the present study was to investigate the immune response induced by Mycobacterium marinum infection in vitro and the potential of M. marinum as an immunotherapy for M. tuberculosis infection.

Methods: The potential human immune response to certain bacillus infections was investigated in an immune cell-bacillus coculture system in vitro. As a potential novel immunotherapy, M. marinum was studied and compared with two other bacilli, Bacillus Calmette-Guérin (BCG) and live attenuated M. tuberculosis. We examined the changes in both the bacilli and immune cells, especially the time course of the viability of mycobacteria in the coculture system and host immune responses including multinuclear giant cell formation by Wright-Giemsa modified staining, macrophage polarization by cell surface antigen expression, and cytokines/chemokine production by both mRNA expression and protein secretion.

Results: The M. marinum stimulated coculture group showed more expression of CD209, CD68, CD80, and CD86 than the BCG and M. tuberculosis (an attenuated strain, H37Ra) groups, although the differences were not statistically significant. Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively). The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1β, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively). In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).

Conclusion: Our results indicated that M. marinum could be a potentially safe and effective immunotherapy.

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Related in: MedlinePlus

The mRNA expression kinetics of cytokines and chemokines was detected by RT-PCR.Notes: (A) The mRNA expression of different cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, and IL-12p40) was detected on day 1, 3, and 7. (B) The mRNA expression of different chemokines (chemokine (C-X-C motif) ligand [CXCL] 8, CXCL10, and chemokine (C motif) ligand 1) was detected on day 1 and 3. The group M+P, M+P+B, and M+B refer to the control group without bacilli, experimental groups, and control groups without peripheral blood mononuclear cells, respectively, while the bacilli B, M, and H refer to Bacillus Calmette-Guérin, M marinum, and H37Ra, respectively.Abbreviations: CXCL, chemokine (C-X-C motif) ligand; IL, interleukin; TNF, tumor necrosis factor; XCL, chemokine (C motif) ligand; RT-PCR, real time polymerase chain reaction.
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f3-dddt-7-669: The mRNA expression kinetics of cytokines and chemokines was detected by RT-PCR.Notes: (A) The mRNA expression of different cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, and IL-12p40) was detected on day 1, 3, and 7. (B) The mRNA expression of different chemokines (chemokine (C-X-C motif) ligand [CXCL] 8, CXCL10, and chemokine (C motif) ligand 1) was detected on day 1 and 3. The group M+P, M+P+B, and M+B refer to the control group without bacilli, experimental groups, and control groups without peripheral blood mononuclear cells, respectively, while the bacilli B, M, and H refer to Bacillus Calmette-Guérin, M marinum, and H37Ra, respectively.Abbreviations: CXCL, chemokine (C-X-C motif) ligand; IL, interleukin; TNF, tumor necrosis factor; XCL, chemokine (C motif) ligand; RT-PCR, real time polymerase chain reaction.

Mentions: The cellular mRNA expression of the cytokines TNF-α, IFN-γ, IL-12p40, and IL-1B was detected by RT-PCR. The TNF-α expression in the M+P+B groups peaked on day 3 with a level higher in the M+P+B−M group than in the M+B−M group (P = 0.017). The IFN-γ expression in the M+P+B groups also peaked on day 3 with a much higher expression in the M+P+B-M group than in the M+P and M+B−M groups (P = 0.000 and 0.000, respectively). The M+P+B−H group also had a higher IFN-γ expression than the M+P and the M+B−H groups (P = 0.000 and 0.000, respectively). Among the three M+P+B groups, the M+P+B−M and the M+P+B−H groups exhibited higher IFN-γ expression than the M+P+B−B group (P = 0.000 and 0.000, respectively). On day 3 and 7, the M+P+B−M group expressed higher levels of IL-12p40 than the M+P+B−B and M+P+B−H groups (day 3: P = 0.001 and 0.011, respectively; day 7: P = 0.001 and 0.000, respectively). The IL-1B expression was highest on day 1 in the M+P+B groups, and higher IL-1B expression was observed in the M+P+B−M group when compared with the M+P, M+B−M, M+P+B−B, and M+P+B−H groups on day 3 (P = 0.021, 0.000, 0.003, and 0.004, respectively) (Table 2 and Figure 3A).


Mycobacterium marinum: a potential immunotherapy for Mycobacterium tuberculosis infection.

Tian WW, Wang QQ, Liu WD, Shen JP, Wang HS - Drug Des Devel Ther (2013)

The mRNA expression kinetics of cytokines and chemokines was detected by RT-PCR.Notes: (A) The mRNA expression of different cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, and IL-12p40) was detected on day 1, 3, and 7. (B) The mRNA expression of different chemokines (chemokine (C-X-C motif) ligand [CXCL] 8, CXCL10, and chemokine (C motif) ligand 1) was detected on day 1 and 3. The group M+P, M+P+B, and M+B refer to the control group without bacilli, experimental groups, and control groups without peripheral blood mononuclear cells, respectively, while the bacilli B, M, and H refer to Bacillus Calmette-Guérin, M marinum, and H37Ra, respectively.Abbreviations: CXCL, chemokine (C-X-C motif) ligand; IL, interleukin; TNF, tumor necrosis factor; XCL, chemokine (C motif) ligand; RT-PCR, real time polymerase chain reaction.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3733875&req=5

f3-dddt-7-669: The mRNA expression kinetics of cytokines and chemokines was detected by RT-PCR.Notes: (A) The mRNA expression of different cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, and IL-12p40) was detected on day 1, 3, and 7. (B) The mRNA expression of different chemokines (chemokine (C-X-C motif) ligand [CXCL] 8, CXCL10, and chemokine (C motif) ligand 1) was detected on day 1 and 3. The group M+P, M+P+B, and M+B refer to the control group without bacilli, experimental groups, and control groups without peripheral blood mononuclear cells, respectively, while the bacilli B, M, and H refer to Bacillus Calmette-Guérin, M marinum, and H37Ra, respectively.Abbreviations: CXCL, chemokine (C-X-C motif) ligand; IL, interleukin; TNF, tumor necrosis factor; XCL, chemokine (C motif) ligand; RT-PCR, real time polymerase chain reaction.
Mentions: The cellular mRNA expression of the cytokines TNF-α, IFN-γ, IL-12p40, and IL-1B was detected by RT-PCR. The TNF-α expression in the M+P+B groups peaked on day 3 with a level higher in the M+P+B−M group than in the M+B−M group (P = 0.017). The IFN-γ expression in the M+P+B groups also peaked on day 3 with a much higher expression in the M+P+B-M group than in the M+P and M+B−M groups (P = 0.000 and 0.000, respectively). The M+P+B−H group also had a higher IFN-γ expression than the M+P and the M+B−H groups (P = 0.000 and 0.000, respectively). Among the three M+P+B groups, the M+P+B−M and the M+P+B−H groups exhibited higher IFN-γ expression than the M+P+B−B group (P = 0.000 and 0.000, respectively). On day 3 and 7, the M+P+B−M group expressed higher levels of IL-12p40 than the M+P+B−B and M+P+B−H groups (day 3: P = 0.001 and 0.011, respectively; day 7: P = 0.001 and 0.000, respectively). The IL-1B expression was highest on day 1 in the M+P+B groups, and higher IL-1B expression was observed in the M+P+B−M group when compared with the M+P, M+B−M, M+P+B−B, and M+P+B−H groups on day 3 (P = 0.021, 0.000, 0.003, and 0.004, respectively) (Table 2 and Figure 3A).

Bottom Line: Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively).The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1β, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively).In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).

View Article: PubMed Central - PubMed

Affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, People's Republic of China.

ABSTRACT

Purpose: The aim of the present study was to investigate the immune response induced by Mycobacterium marinum infection in vitro and the potential of M. marinum as an immunotherapy for M. tuberculosis infection.

Methods: The potential human immune response to certain bacillus infections was investigated in an immune cell-bacillus coculture system in vitro. As a potential novel immunotherapy, M. marinum was studied and compared with two other bacilli, Bacillus Calmette-Guérin (BCG) and live attenuated M. tuberculosis. We examined the changes in both the bacilli and immune cells, especially the time course of the viability of mycobacteria in the coculture system and host immune responses including multinuclear giant cell formation by Wright-Giemsa modified staining, macrophage polarization by cell surface antigen expression, and cytokines/chemokine production by both mRNA expression and protein secretion.

Results: The M. marinum stimulated coculture group showed more expression of CD209, CD68, CD80, and CD86 than the BCG and M. tuberculosis (an attenuated strain, H37Ra) groups, although the differences were not statistically significant. Moreover, the M. marinum group expressed more interleukin (IL)-1B and IL-12p40 on day 3 (IL-1B: P = 0.003 and 0.004, respectively; IL-12p40: P = 0.001 and 0.011, respectively), a higher level of CXCL10 on day 1 (P = 0.006 and 0.026, respectively), and higher levels of chemokine (C-X-C motif) ligand (CXCL) 8 and chemokine (C motif) ligand (XCL) 1 on day 3 (CXCL8: P = 0.012 and 0.014, respectively; XCL1: P = 0.000 and 0.000, respectively). The M. marinum stimulated coculture group also secreted more tumor necrosis factor (TNF)-α, IL-1β, and IL-10 on day 1 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.000, respectively; IL-10: P = 0.002 and 0.019, respectively) and day 3 (TNF-α: P = 0.000 and 0.000, respectively; IL-1β: P = 0.000 and 0.001, respectively; IL-10: P = 0.000 and 0.000, respectively). In addition, the colony-forming units (an index of viability) of M. marinum in the M. marinum stimulated coculture group was significantly less than that of BCG and H37Ra in their corresponding bacillus stimulated groups (P = 0.037 and 0.013, respectively).

Conclusion: Our results indicated that M. marinum could be a potentially safe and effective immunotherapy.

Show MeSH
Related in: MedlinePlus