E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

 WNT signatures are an integral part of macrophage responses to infection (#268)

Johanna K Ljungberg 1 , Rhiannon Bolton 1 , Rachel F Rollo 1 , Meg L Donovan 1 , Timothy J Wells 1 2 , Antje Blumenthal 1 2
  1. University of Queensland, Diamantina Institute, Brisbane, QLD, Australia
  2. Australian Infectious Diseases Centre, University of Queensland, Brisbane, QLD, Australia

Actionable molecular targets for host-directed interventions in challenging bacterial infections are the subject of intense investigation.  The WNT signalling network has emerged as an integral component of host responses to bacterial infection. With roles in shaping immune functions such as inflammatory cytokine responses and cellular antimicrobial defense, WNT signalling is being explored as a potential target for tailoring immune responses. As our understanding of immune-related WNT functions is evolving rapidly and some evidence suggests that pathogens may actively manipulate WNT-controlled cellular functions, it is now important to delineate factors that define the nature of the WNT response to infection. To address this, we profiled WNT responses in macrophages upon infection with phylogenetically diverse bacterial pathogens. We observed that a subset of the 19 mammalian WNT ligands was differentially expressed upon bacterial infection, with substantial similarities WNT responses induced by extracellular and intracellular Gram-positive and -negative bacteria. WNT responses induced by viable compared to killed bacteria were identical, indicating that active modulation of macrophage WNT expression is not a common feature of bacterial pathogens. In line with these observations, we identified TLR signalling as a major molecular driver of macrophage WNT responses. As we expand these studies, our findings to date indicate that macrophage WNT responses are controlled by classical innate immune recognition mechanisms, resulting in WNT responses that might be indicative of infection, without revealing distinct signatures for different groups of bacterial pathogens. This has important implications for the understanding of how WNT ligands contribute to the host response to bacterial infection and how this might be exploited for the design of WNT-targeting strategies.