Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB/c and C57Bl/6 mice.
Melioidosis is caused by the Gram-negative bacterium Burkholderia pseudomallei, whose portals of entry into the body include subcutaneous, ingestion and inhalation routes. Animal models play an important role in furthering our understanding of this disease, which is associated with high morbidity and mortality in susceptible subjects. Previous studies using intranasal inoculation showed a differential susceptibility to inhalational melioidosis in BALB/c and C57Bl/6 mice and attributed the difference to genetic factors and host response. However, a recent study found no difference in susceptibility when the two species of mice were exposed to nebulized bacteria. We sought to address this discrepancy by using a nasal route only, instead of whole-body aerosol exposure system. Employing three different clinical strains of B. pseudomallei and following the progression of disease development in both BALB/c and C57Bl/6 mice, we found that BALB/c mice were at least 10- to 100-fold more susceptible to infection than C57Bl/6 mice. Comparison of bacterial burdens in aerosol-challenged mice, at both the pulmonary and distant sites of infection, suggests that C57Bl/6 mice were more efficient in clearing the bacteria than BALB/c mice. In addition, a comprehensive study of a wide panel of chemokines and cytokines at the protein level demonstrated that hyperproduction of proinflammatory cytokines in aerosol-challenged BALB/c mice did not translate into better protection and survival of these mice, whereas a moderate increase in these proteins in aerosol-challenged C57Bl/6 mice was more beneficial in clearing the infection. This suggests that high levels of proinflammatory cytokines are detrimental and contribute to the immunopathogenesis of the infection.
Tan
Gek-Yen Gladys
GG
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
Liu
Yichun
Y
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
Sivalingam
Suppiah Paramalingal
SP
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
Sim
Siew-Hoon
SH
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
Wang
Dongling
D
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
Paucod
Jean-Charles
JC
Centre de Recherches du Service de Santé des Armées Emile Pardé, La Tronche, France.
Gauthier
Yves
Y
Centre de Recherches du Service de Santé des Armées Emile Pardé, La Tronche, France.
Ooi
Eng-Eong
EE
Medical Countermeasures Laboratory, DSO National Laboratories, Singapore 117510.
D000336:Aerosols; D000818:Animals; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D008554:Melioidosis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000336:Aerosols; D016207:Cytokines