The

genetic basis for the aberrant immune response in susceptible individuals is not clearly defined. Several years ago we discovered that inbred strains of mice vary over 4 logs in their susceptibility to infection with C. immitis and that resistance is the dominant phenotype [10]. This proved to be a polygenic trait, and a resistance locus was identified on chromosome 6 using recombinant inbred BXD lines [11]. C57BL/6 mice are more sensitive to infection with C. immitis than DBA/2 mice such that nearly all C57BL/6 mice die between day 16 and 18 post-infection [10]. We have shown that infected C57BL/6 mice make more IL-10 and IL-4 and less interferon gamma (IFN-γ) in their lungs compared to DBA/2 mice [12]. IL-10 has pleiotropic effects on Selleckchem Tamoxifen different cell types that affect the acquired immune response

resulting in inhibition of the development of Th1 immune responses [13]. In the current work, microarray analysis was used to identify genes differentially expressed between lung tissue samples from resistant DBA/2 and sensitive C57BL/6 mice following infection with C. immitis. Differentially expressed genes were mapped onto biological pathways, gene ontologies and protein networks in order to fully characterize the biological processes HDAC inhibitors in clinical trials that contribute to a protective response against C. immitis infection. Results C. immitis infection in DBA/2 resistant versus sensitive C57BL/6 mice The colony forming units (CFUs) in the right (R) lung and spleen of DBA/2 and C57BL/6 mice were determined after intra-nasal (i.n.) infection with C. immitis arthroconidia. We chose three time points after infection ADP ribosylation factor for analysis

(day 10, 14 and 16). Since mice were only infected with 50 CFU and not all of them were inhaled, day 10 is the earliest day when there are enough organisms in the lungs to reliably quantitate pulmonary infection in all mice. C57BL/6 mice began to die on day 16 so this was selected as the last time point, and day 14 was chosen as an intermediate time point. On day 10 after infection there were equal numbers of CFU in the lungs of both strains of mice and we could not detect dissemination by culturing their spleens (Figure 1). On day 14 and 16 post-infection DBA/2 mice had 10 to 100 fold fewer CFU/lung, and in this experiment no DBA/2 mice had detectable dissemination to the spleen, whereas all the C57BL/6 mice had positive spleen cultures. Figure 1 Comparison of C. immitis infection between resistant DBA/2 and sensitive C57BL/6 mice. Mice were infected (i.n.) and then sacrificed at the indicated intervals. The right lung and spleen of each mouse was homogenized and cultured quantitatively. Each symbol represents an individual mouse and the horizontal lines are the geometric mean ± standard error of the mean.