Recognition of pathogenic bacteria by intestinal stem cells promotes adult Drosophila midgut regeneration.

When enteropathogenic bacteria breach the intestinal epithelium, they are recognised by epithelial and immune cells that elicit an intestinal regenerative response. However, less is known about whether and how intestinal stem cells (ISCs) directly detect invading pathogenic bacteria and couple this to their proliferation. Here, we show that adult Drosophila midgut ISCs recognise pathogenic bacteria through the peptidoglycan recognition proteins, PGRP-LC and PGRP-LE, and translate this into their proliferation by stimulating Imd-Mkk3-p38 signalling. Moreover, we find that PGRP-LC/LE-Imd-Mkk3-p38 signalling in ISCs regulates p38 activation throughout the midgut epithelium after infection, indicating that ISCs can influence the regenerative microenvironment in a non-cell autonomous manner. Whilst it was previously thought that ISC proliferation in both mammals and flies is driven solely by damage-induced signals after infection, our work reveals that ISCs can directly recognise pathogenic bacteria and mount a strong parallel regenerative response that spreads throughout the midgut epithelium. Increased ISC proliferation after bacterial recognition may also serve as a strategy to repopulate the epithelium with uninfected cells.