The host response to bacterial infection is influenced by many miRNAs, and there is great interest in miRNAs for use as biomarkers and treatments of infectious disease. Previous studies in our group have identified an association with miR-652 and intracellular infection. Using a miR-652-/- mouse model, we investigated the impact of miR-652 on the immune response to infection with the acute intracellular pathogen Listeria monocytogenes.
Wild type and miR-652-/- mice were subject to intraperitoneal infection with L. monocytogenes and the host immune response were quantitated through flow-cytometric analysis and visualised by H&E histology.
miR-652-/- mice showed significantly increased mortality 3 days after low-dose L. monocytogenes infection, with 38% survival after 7 days, compared to 93% survival in wild type mice. Mice euthanised for ethical reasons were deemed susceptible, and the remaining mice resistant. Susceptible miR-652-/- mice presented notably higher bacterial count in the liver and spleen at 4 days post-infection. Additionally, histology showed larger and more numerous lesions in the livers of susceptible mice. Bacterial counts in resistant miR-652-/- mice were not different from wild type mice. Significantly greater CD8+ CD44+ CD62L- and CD4+ CD44+ CD62L- effector T cells were present in the spleen of miR-652-/- mice 10 days post-infection.
The mechanism by which miR-652 ensures protection during L. monocytogenes infection is being elucidated, though the onset of mortality before the typical T cell peak response at 7 days post-infection suggests the effect is related to induction of a protective innate immune response.