Immune reactions against pathogens and tumours require several layers of regulation to ensure the appropriate control of infectious agents and cancerous cells without inducing excessive tissue damage or inflammation.  In the last decade we have begun to recognise that peripheral neurons establish a reciprocal molecular and signalling dialogue with immune cells, and that this conversation can significantly and critically impact the result of immune responses.  However, our understanding of how this neuroimmune crosstalk is regulated and the details of which neurons, immune cells and molecules participate in it are still superficial.

This project seeks to explore and determine which neuronal-derived cues modulate immune cells in the context of viral infections and cancer at mucosal tissues such as the lung, the intestine or the female reproductive tract.  Using transgenic mouse strains, mouse models of viral infection and/or tumorigenesis, and precise targeting of sensory and motor neurons, the project aims to define and dissect the neuroimmune cellular axes and molecular signalling pathways impacting immune system homeostasis and immunity. Initially, the project will concentrate on developing and implementing optogenetic and chemogenetic approaches to modulate peripheral neurons (e.g., vagal afferent and efferent neurons) innervating mucosal tissues. Immune cells, with particular focus on lymphocytes, will be extensively characterise by high-dimensional flow cytometry, omics analysis, and in vivo and in vitro approaches. Newly uncovered cellular and molecular pathways will be functionally characterised and perturb to study their impact in cancer and viral infections.

We expect that the results derived from this project will aid in our understanding of neuro-immune homeostasis, how they neuro-immune crosstalk can impact health and disease, and lead to exciting discoveries at the physiological and molecular level.

For project inquiries please contact Andrew McKenzie or Noe Rodriguez. For application process enquiries please contact the Postgraduate Ofiice.

References

Cohen et al Cutaneous TRPV1⁺ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity 2019, Cell

Rodriguez-Rodriguez et al, Group 2 Innate Lymphoid Cells: Team Players in Regulating Asthma Annu Rev Immunol

Jou et al. An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis. 2022 Sci Immunol

Balood et al Nociceptor neurons affect cancer immunosurveillance 2023, Nature