Early Host Response To Infection Is Influenced By The Listeria Monocytogenes Broad-Range Phospholipase C
Listeria monocytogenes is a facultative intracellular bacterial pathogen that causes disease in humans and animals. A mutant strain that has lost the ability to control the activity of a phospholipase C is attenuated in mice. This attenuation is not due to a lack of bacterial fitness, but appears to result from a modified immune response to infection. In a competitive assay, the mutant strain compromises the ability of wild-type (wt) L. monocytogenes to multiply in the liver of infected animals. To assess how the mutant modifies the hepatic immune response to infection, we monitored the kinetics of immune cell recruitment in the liver of infected mice and levels of serum inflammatory cytokines up to three days post-infection. At day 3, an increase in neutrophils was only detected in wild-type infected mice, whereas an increase in dendritic cells was only detected in mutant infected mice. Other innate immune cell types were recruited to the same levels in mice infected with either wt or mutant bacteria. Interferon gamma was detected in the serum of mice infected with wt bacteria at day 1-3 post-infection, but only at day 2 postinfection in mice infected with the mutant strain. Interleukin 12 was only detected in mice infected with wt bacteria. Also, transcriptional profiling of macrophages indicated that immune related genes were similarly up-regulated within both mutant and wt infections, while varying regulation of pathways revealed possible differences in host response to infection. At 60 minutes post infection mutant bacteria demonstrated increased efficiency at vacuolar escape and decreased mitochondrial damage at 90 minutes versus wt. Together, these results suggested that PC-PLC potentiates the host ability to clear L. monocytogenes in a way that does not involve an increase in the inflammatory response to infection.
Listeria monocytogenes; Phospholipase C; Host response
M.S., Veterinary Medicine
Master of Science
dissertation or thesis