Mycobacterium marinum: a potential immunotherapy for Mycobacterium tuberculosis infection.
OBJECTIVE
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).


CONCLUSIONS
Our results indicated that M. marinum could be a potentially safe and effective immunotherapy.
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.
Wei-wei
WW
Tian
Qian-qiu
QQ
Wang
Wei-da
WD
Liu
Jian-ping
JP
Shen
Hong-sheng
HS
Wang
D002449:Cell Aggregation; D018925:Chemokines / Q000235:genetics; D002675:Child, Preschool; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D006099:Granuloma / Q000382:microbiology; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D007231:Infant, Newborn; D019910:Mycobacterium marinum / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D014376:Tuberculosis / Q000628:therapy*
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger
Mycobacterium marinum; bacilli; immunity; immunotherapy