Leo James

Intracellular immunity

Despite extracellular immune surveillance, many viral and bacterial pathogens are still able to infect cells. Because of this there must be a way to detect and neutralise pathogens intracellularly. Historically, infected cells have been seen as largely helpless and only able to signal for help. However, there is increasing evidence that cells have their own mechanisms for directly restricting pathogen replication.

Intracellular Humoral Immunity. (A) Antibody-coated virions that infect the cell and enter the cytosol are detected by the Fc receptor and E3 ubiquitin ligase TRIM21. TRIM21 mediates rapid degradation of the virus in a process involving the segregase/unfoldase VCP and the proteasome, thereby preventing its replication. TRIM21 also catalyses the formation of K63 ubiquitin chains and stimulates immune transcription pathways (NFκB is shown but AP-1 and IRF/3/5/7 pathways are also activated). (B) Complement C3 that covalently deposits onto virus is also carried into the cell during infection where it also activates dual effector and signalling responses. The receptor for C3 is unknown but downstream adaptors MAVS and TRAFs are required. The two intracellular humoral immune pathways posses both similarities and differences.


It is this process of intracellular immunity that my lab is interested in. In order to study intracellular immunity, we are combining cellular pathogen infection experiments with structural and biophysical approaches. We use these techniques to investigate infection from both the host and pathogen perspective. The evolutionary arms race between the two continues to provide some of the most unexpected and fascinating discoveries in biology and these insights form the basis of future medicines and therapies.

Pathogens exploit cellular cofactors to promote infection. The HIV-1 capsid
recruits cofactors CPSF6 and NUP153 to promote infection


Before pathogens can be neutralised they must first be detected.
Antibody coated salmonella detected by TRIM21


Overview of intracellular immunity provided by TRIM21

Selected Papers

Group Members

  • Donna Mallery
  • Marina Vaysburd
  • William McEwan
  • Dean Clift
  • David Jacques
  • Maria Bottermann
  • Adam Fletcher
  • Claire Dickson
  • Sarah Caddy
  • Larisa Labzin
  • Jingwei Zeng