The role of reactive oxygen intermediates in experimental coccidioidomycois in mice
1 Veterans Affairs San Diego Healthcare System (111F) 3350 La Jolla Village Dr, San Diego, CA 92161, USA
2 Veterans Medical Research Foundation, 3350 La Jolla Village Dr. San Diego, CA 92161, USA
3 Department of Pathology University of California, San Diego, San Diego, California, 92093, USA
4 Department of Medicine, University of California, San Diego, San Diego, California, 92093 USA
5 GlaxoSmithKline Infectious Diseases Medicine Development Center 5 Moore Drive Research Triangle Park, NC 27709 USA
BMC Microbiology 2011, 11:71 doi:10.1186/1471-2180-11-71Published: 11 April 2011
Coccidioidomycosis is usually a self-limited infection in immunocompentent people. In immunocompentent human beings second infections due to Coccidioides are very rare, indicating that recovery from infection results in protective immunity. In experimental animals, immunization with several different proteins or attenuated mutants protects against a virulent challenge. To explore what mechanisms are responsible for protective immunity, we investigated the course of Coccidioides infection in the gp91phox knock out mouse that has a defect in the oxidative burst that results in chronic granulomatous disease.
We found that the gp91phox knock out mice were somewhat more resistant to intraperitoneal infection and equally as resistant to low dose intranasal infection, but slightly more susceptible to high dose intranasal infection compared to control mice. The gp91phox knock out mice made a more robust inflammatory response to infection than controls, as measured by histology and production of inflammatory cytokines. The gp91phox knock out mice were as protected by immunization with the recombinant Coccidioides protein Ag2/PRA as the controls were against either intraperitoneal or intranasal infection. Coccidioides immitis arthroconidia and spherules were significantly more resistant to H2O2 treatment in vitro than Aspergillus fumigatus spores.
These data suggest that oxidative burst may not be required for protective immunity to coccidioidomycois.