Trained immunity and Phagocytosis

 

Hull York Medical School, York Biomedical Research Institute, University of York, United Kingdom. 

 

Research topic

Chronic inflammation is associated with increased rates of morbidity and mortality worldwide thus having long-lasting socioeconomic impact. Exposure of the host to certain microbial components induces a type of memory to the immune system termed innate immune memory (IIM) that enhances clearance of subsequent infections. The exciting concept of IIM impacts our current way of understanding on host defence and has important implications on disease pathophysiology.

Myeloid cells represent a key immune cell type for shaping IIM and demonstrate functional plasticity depending on the inflammatory stimulus to which is exposed. This is important because certain types of myeloid cells represent professional “eaters” that remove intruding pathogens and cells that have died during inflammation. This well-coordinated process of recognition and engulfment of “foreign” material by myeloid cells termed phagocytosis is of paramount importance in tissue repair and disease clearance. Interestingly, impaired phagocytosis drives chronic destructive inflammation and disease pathogenesis. Our research focus lies in the investigation of mechanisms orchestrating phagocytosis in the context of IIM.

 

Group leader

Dr. Ioannis Kourtzelis

 

Group members

Alexandros Chatzis, PhD student

 

Selected publications

  • Innate immune training of granulopoiesis promotes anti-tumor activity. Cell, 2020.
  • DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat. Immunol. 2019.
  • Modulation of haematopoietic progenitors is an integral component of trained immunity. Cell. 2018.
  • The mevalonate pathway drives metabolic and epigenetic reprogramming during induction of trained immunity. Cell. 2018.
  • Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche. J Clin Invest. 2017.
  • Phagocytosis of Apoptotic Cells in Resolution of Inflammation. Front Immunol. 2020
  • From leukocyte recruitment to resolution of inflammation: the cardinal role of integrins. J Leukoc Biol. 2017.
  • The dual role of complement in cancer and its implication in anti-tumor therapy. Ann Transl Med. 2016.

 

Financial support

  • Royal Society grant
  • University of York