Mycobacterium marinum: a potential immunotherapy for Mycobacterium tuberculosis infection

Abstract

PurposeThe 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.MethodsThe 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.ResultsThe 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).ConclusionOur results indicated that M. marinum could be a potentially safe and effective immunotherapy.

Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review

“…The quantification of changes in expression of M1/M2 markers is feasible via flow cytometric analysis since most studies compared the expression levels of both [ 5 , 10 , 12 , 27 , 44 , 45 , 49 , 50 , 51 ].…”

“…Significantly increased expression was observed for several markers: CD68 + expression levels increased, especially when tested with mycobacterial antigens [ 5 , 51 ]. CD86 + and HLA-DR expression levels on macrophages were significantly elevated regardless of the antigen that was used.…”

“…The following changes in expression were reported for M2 macrophage surface markers in mycobacterial granulomas: CD163 + [ 28 ] and CD206 + [ 12 ] showed an insignificant and significant decrease in expression, respectively. CD209 + [ 51 ] expression remained unchanged. …”

Skin and subcutaneous infections in south-east Asia

“…Common disinfectants such as ethyl alcohol, benzyl-4-chlorophenol and sodium chlorite have been shown to be the most effective to reduce or eliminate the organism from an aquarium or aquaculture facility [77]. There are no vaccines available but research on the use of M. marinum as potential immunotherapy for tuberculosis is under way [78].…”

Formulation and in vitro characterization of rifampicin-loaded porous poly (ε-caprolactone) microspheres for sustained skeletal delivery

“…Mycobacterium tuberculosis (MTB) is a serious public health problem affecting hundreds of millions of elderly people worldwide, with nearly one-third of the global population infected by MTB and latent MTB infection. 1 , 2 It is worth noting that the skeletal system was involved in 1%–3% of tuberculosis (TB) cases, and extraspinal TB could cause osteomyelitis or arthritis in any peripheral bones or joints. 3 , 4 Currently, surgical intervention has been developed as a general rule for osteoarticular TB treatment.…”