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Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas

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Abstract
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 immunosuppresive 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.
Keywords
Buruli ulcer, animal model, cytokines, immunopathology, Mycobacterium ulcerans, GROWTH-FACTOR-BETA, ANTIMICROBIAL PEPTIDES, MACROLIDE TOXIN, BURULI-DISEASE, T-CELLS, INFECTION, TUBERCULOSIS, MYCOLACTONE, APOPTOSIS, INTERFERON

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MLA
Hurtado Ortiz, R et al. “Differences in Virulence and Immune Response Induced in a Murine Model by Isolates of Mycobacterium Ulcerans from Different Geographic Areas.” CLINICAL AND EXPERIMENTAL IMMUNOLOGY 157.2 (2009): 271–281. Print.
APA
Hurtado Ortiz, R., Aguilar Leon, D., Orozco Estevez, H., Martin, A., Luna Herrera, J., Flores Romo, L., Portaels, F., et al. (2009). Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 157(2), 271–281.
Chicago author-date
Hurtado Ortiz, R, D Aguilar Leon, H Orozco Estevez, Anandi Martin, J Luna Herrera, L Flores Romo, F Portaels, and R Hernandez Pando. 2009. “Differences in Virulence and Immune Response Induced in a Murine Model by Isolates of Mycobacterium Ulcerans from Different Geographic Areas.” Clinical and Experimental Immunology 157 (2): 271–281.
Chicago author-date (all authors)
Hurtado Ortiz, R, D Aguilar Leon, H Orozco Estevez, Anandi Martin, J Luna Herrera, L Flores Romo, F Portaels, and R Hernandez Pando. 2009. “Differences in Virulence and Immune Response Induced in a Murine Model by Isolates of Mycobacterium Ulcerans from Different Geographic Areas.” Clinical and Experimental Immunology 157 (2): 271–281.
Vancouver
1.
Hurtado Ortiz R, Aguilar Leon D, Orozco Estevez H, Martin A, Luna Herrera J, Flores Romo L, et al. Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas. CLINICAL AND EXPERIMENTAL IMMUNOLOGY. 2009;157(2):271–81.
IEEE
[1]
R. Hurtado Ortiz et al., “Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas,” CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol. 157, no. 2, pp. 271–281, 2009.
@article{7187314,
  abstract     = {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 immunosuppresive 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.},
  author       = {Hurtado Ortiz, R and Aguilar Leon, D and Orozco Estevez, H and Martin, Anandi and Luna Herrera, J and Flores Romo, L and Portaels, F and Hernandez Pando, R},
  issn         = {0009-9104},
  journal      = {CLINICAL AND EXPERIMENTAL IMMUNOLOGY},
  keywords     = {Buruli ulcer,animal model,cytokines,immunopathology,Mycobacterium ulcerans,GROWTH-FACTOR-BETA,ANTIMICROBIAL PEPTIDES,MACROLIDE TOXIN,BURULI-DISEASE,T-CELLS,INFECTION,TUBERCULOSIS,MYCOLACTONE,APOPTOSIS,INTERFERON},
  language     = {eng},
  number       = {2},
  pages        = {271--281},
  title        = {Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2009.03941.x},
  volume       = {157},
  year         = {2009},
}

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