Cambridge Institute for Medical Research

Dr Andres Floto

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Antigen processing by macrophages and dendritic cells.

Research Interests

We are interested in understanding how antigen processing is controlled by macrophages and dendritic cells and how it may be dysregulated in autoimmune disease and subverted by pathogenic bacteria.
Our research is focused on three interrelated areas:

1. Control of phagosomal function.

Particulate antigen and bacteria are internalised into a membrane compartment known as the phagosome that successively fuses with early and late endosomes and finally lysosomes. The behaviour of the phagosome regulates cargo degradation and bacterial killing, cytosolic export of antigen for cross-presentation and inflammasome activation. Using a variety of live cell imaging, cellular and biochemical techniques, we are examining how i) signalling from Fcg receptors (FcgRs), Toll-like receptors (TLRs) and scavenger receptors interact to control phagosomal function in human macrophages and dendritic cells; ii) how ion channels and transporters modulate phagosomal pH and peri-phagosomal calcium levels to control cargo degradation and lysosomal fusion; iii) how macro-autophagy pathways interact with phagosomes to determine functional outcomes and iv) how GPCRs and tyrosine kinase receptors may influence antigen processing and effector responses.

2. Mycobacterial infection

We are studying how M. tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) interact with macrophages and dendritic cells particularly: i) defining novel host factors controlling bacterial detection, intracellular killing and antigen presentation (through functional screening of genes identified from genetic studies); ii) examining whether therapeutic enhancement of autophagy can be used to improve intracellular killing and how inadvertent pharmacological block of autophagy might predispose to NTM infection; iii) In collaboration with Dr M. Noursadeghi (UCL), we are examining the influence of HIV co-infection on macrophage responses to intracellular MTB and iv) identifying new genetic determinants controlling the pathogenesis of the NTM species M. abscessus through the combination of whole genome sequencing (in collaboration with Julian Parkhill, WTSI), in vitro functional phenotyping and clinical disease characteristics

3. Pneumococcal infection

Together with Dr Jerry Brown (UCL), we are aiming to understand how Streptococcus pneumoniae polysaccharide capsules influences FcgR-dependent and independent uptake and subsequent antigen processing.

 

Funding

• Wellcome Trust
• Medical Research Council
  
• NIHR Cambridge Biomedical Research Centre
  
• Papworth Hospital
  
• Health Enterprise East SBRI

Group Members