Heterogeneous Host-Pathogen Encounters: Act Locally, Think Globally

Recent studies are revealing astonishing heterogeneity in host-pathogen interactions occurring simultaneously within the same host tissue. As highlighted in this review, growing knowledge of the in vivo complexity is altering our understanding of infection biology. In particular, pathogen subsets reside in diverse tissue microenvironments and detect and respond to local conditions. The individual pathogen-host encounters have disparate outcomes, depending on differential molecular interactions. As a result, disease progression can result from failure to control individual infection foci, despite successful eradication of others, and antibiotic therapy can be delayed by distinct pre-existing pathogen subsets. Together, these data are unraveling rich biology with implications for infectious disease progression and control.