Coxiella burnetii and Leishmania mexicana residing within similar parasitophorous vacuoles elicit discordant host responses.

Coxiella burnetii is the only bacterium known to thrive in an acidic intracellular vacuole derived from lysozomes. Leishmania mexicana, a eukaryote, has also independently evolved to live in a morphologically similar vacuole. As Coxiella and Leishmania are distantly related, we hypothesized that their respective infections will elicit disparate host responses while producing similar parasite-containing vacuoles, thereby revealing the host processes targeted by each pathogen. We studied this parallel evolution of host cell regulation by comparing gene expression in human cells infected with C. burnetii or L. mexicana. At 5 d post-infection, negative regulation of cell death was observed in C. burnetii infected cells--probably to prolong host cell life cycle to enhance bacterial replication; conversely, positive regulation of cell death was upregulated in L. mexicana infection--probably to promote pathogen cell-to-cell spread. In concert with these observations, C. burnetii and L. mexicana also altered the expression of host microRNAs that modulate apoptosis. Intriguingly, several host genes displayed differential expression of mRNA isoforms, suggestive of diverse functions for the encoded proteins. By comparing host responses to Coxiella and Leishmania infections, we are beginning to understand the evolutionary processes that enabled a bacterium and a eukaryote to occupy the same extreme environment.