Host gene expression responses can be used to determine the etiology of acute infection. PBMCs were stimulated with bacterial, viral, and fungal stimuli and then analyzed for differential gene expression utilizing microarrays to derive pathogen class-specific gene expression classifiers of infection. Discovery Cohort: In vitro human PBMC challenges were performed with bacteria (gram postive and gram negative), viruses (4 strains of influenza), and fungi (Cryptococcus and Candida) Overall design: In vitro human PBMC challenges were performed with bacteria (gram postive and gram negative), viruses (4 strains of influenza), and fungi (Cryptococcus and Candida). Exposed human cells were then analyzed for differential gene expression utilizing Affymetrix microarrays to derive pathogen class-specific gene expression classifiers.