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Patrick Mitchell is uncovering strategies that animal cells use to specifically detect pathogens via the innate immune detection of activities that are unique to pathogens. Self- versus non-self-discrimination ensures the appropriate activation of host immunity. These molecular recognition events sense microbial threats by detecting microbe-specific patterns. However, these ubiquitous microbial cues fail to distinguish between ‘true’ pathogens and harmless or even beneficial microbes. Mitchell hopes that understanding the principles of this mode of innate immune recognition, and how they have been shaped by host-pathogen genetic conflicts, will reveal new therapeutic strategies to bolster host defense and dampen auto-inflammatory diseases.