The only significant difference documented between the two routes of infection so far is that some vaccines that

are protective in the intraperitoneal model are not protective in the intranasal model [24]. C57BL/6 mice are extremely susceptible to intranasal infection with Coccidioides so that very small difference in inoculum can have major effects on mortality eFT-508 rate. We have found that the intraperitoneal route of infection is more reproducible and predictable, so we chose to do preliminary experiments using this model. In both these infection models, the gp91 phox mutation had no effect on acquired immunity to Ag2/PRA. These data suggest that reactive oxygen intermediates may not be required for protective immunity. The situation in non-immune mice is less clear. In the intraperitoneal model of infection, the gp91phox KO mice had significantly fewer organisms in their lungs compared to the controls. This may be due to the more exuberant inflammatory response seen in the gp91phox KO mice compared to the B6, as measured by histology and amount of Th1 and Th17 cytokine mRNA in the infected lung. In the intranasal model of infection, no difference between the gp91phox KO and B6 was seen when the mice were challenged with 150 arthroconidia, but there was a small difference

in survival between the two mouse strains when they were challenged BI 10773 mouse with a larger number of organisms. The increased mortality rate may also be due to a more vigorous inflammatory response in the gp91phox KO mice. We also found that C. immitis arthroconidia and spherules were significantly more resistant to killing by H2O2 than Aspergillus fumigatus spores. gp91phox KO mice are susceptible

to pulmonary Aspergillus infection, so this is a potential explanation for the difference in susceptibility of Buspirone HCl the gp91phox KO to these two fungi. However, since it is not clear that ROI kill fungi directly (see below) the significance of this observation is not clear. More studies in CGD mice have been done with the gp47phox KO rather than the gp91phox KO. Mice with both mutations have the CGD phenotype but there may be differences between the two. The observation that gp47phox KO and gp91phox KO mice make a more robust inflammatory response than control mice with an intact respiratory burst has been previously made in mice experimentally infected with Aspergillus fumigatus [25] or in mice given intra-tracheal zymosan [26, 27]. The mechanism of this Selleckchem LY3039478 exaggerated inflammatory response to Aspergillus fumigatus infection was thought to be a defect in a superoxide dependent step in tryptophan metabolism [26]. The exaggerated response to zymosan in gp47phox mice was thought to be due to a failure to activate Nrf2, a redox-sensitive anti-inflammatory regulator [26]. The mechanism by which phagocytes inhibit and damage fungi is complex.