ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

miR-652 deletion impacts immune response to intracellular bacterial infection (#271)

Maxwell Stevens 1 , Samuel Hansen 1 , Matt Padula 1 , Bernadette Saunders 1 2
  1. University of Technology Sydney, Ultimo, NSW, Australia
  2. Centenary Institute, Sydney, NSW, Australia

miRNA are known to impact the host immune response to bacterial infections, making them interesting targets for use in disease treatment and diagnostics. Our group has identified an association between miR-652 and intracellular infection. We investigated the impact of miR-652 deletion on the immune response to infection with the intracellular pathogen Listeria monocytogenes.

Following intraperitoneal L. monocytogenes infection, miR-652-/- mice displayed significantly increased weight loss and mortality, with only 38% survival at 7 days, compared with 93% survival in wild type mice.

Primary peritoneal macrophages were isolated from wild type and miR-652-/- mice and infected with L. monocytogenes for 48 hours in vitro. While wild type and miR-652-/- macrophages controlled L. monocytogenes growth comparably, proteomic analysis showed marked differences in gene expression. This included decreased expression of CAPZB, an in silico predicted target of miR-652 with known activity in intracellular Listeria motility. Also downregulated in miR-652-/- cells were proteins with demonstrated roles in TLR-trafficking to the cell surface including cathepsin B, cathepsin D, and cathepsin Z.

To investigate the role of miR-652 in TLR responses, bone marrow-derived macrophages were incubated with Pam3CSK4 and ODN1585 to stimulate TLR2 and TLR9, respectively. miR-652-/- macrophages showed reduced proinflammatory responses, secreting significantly less IL-6 and TNF compared to wild-type cells.

These data demonstrate that miR-652 influences multiple immunological pathways and is required for a protective host response to Listeria infection. The association between miR-652 and cathepsin regulation is being elucidated, but may represent a new pathway for treatment for intracellular bacterial infections.

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  2. Qi RS, Singh D, Kao CC. Proteolytic Processing Regulates Toll-like Receptor 3 Stability and Endosomal Localization. J Biol Chem 2012; 287: 32617-32629.