Stem cells in the shoot apical meristem (SAM) of plants are the self-renewable reservoir for leaf, stem and flower organogenesis(1,2). In nature, disease-free plants can be regenerated from SAM despite infections elsewhere, which underlies a horticultural practice for decades(3). However, the molecular basis of the SAM immunity remains unclear. Here we show that the CLAVATA3 peptide (CLV3p), expressed and secreted from stem cells and functioning as a key regulator of stem-cell homeostasis in the SAM of Arabidopsis(1,2,4), can trigger immune signalling and pathogen resistance via the flagellin receptor kinase FLS2 (refs 5, 6). CLV3p-FLS2 signalling acts independently from the stem-cell signalling pathway mediated through CLV1 and CLV2 receptors(1,2,4), and is uncoupled from FLS2-mediated growth suppression(5,6). Endogenous CLV3p perception in the SAM by a pattern recognition receptor for bacterial flagellin, FLS2, breaks the previously defined self and non-self discrimination in innate immunity(6,7). The dual perception of CLV3p illustrates co-evolution of plant peptide and receptor kinase signalling for both development and immunity. The enhanced immunity in SAM or germ lines may represent a common strategy towards immortal fate in plants and animals(1,2,8).