Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas.
Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.
Ortiz
R Hurtado
RH
Department of Immunology, National School of Biological Sciences, IPN, Mexico City, Mexico.
Leon
D Aguilar
DA
Estevez
H Orozco
HO
Martin
A
A
Herrera
J Luna
JL
Romo
L Flores
LF
Portaels
F
F
Pando
R Hernandez
RH
D000818:Animals; D001315:Australia; D001541:Benin; D054312:Buruli Ulcer / Q000276:immunology*; D003114:Colony-Forming Units Assay; D003223:Congo; D007560:Cote d'Ivoire; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005869:Ghana; D007564:Japan; D008296:Malaysia; D008297:Male; D008800:Mexico; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology; D019911:Mycobacterium ulcerans / Q000472:pathogenicity*; D010219:Papua New Guinea; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013045:Species Specificity; D014300:Trinidad and Tobago; D014774:Virulence / Q000235:genetics; D023083:beta-Defensins / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D023083:beta-Defensins