The use of adult Drosophila melanogaster as a model for hematopoiesis or organismal
immunity has been debated. Addressing this question, we identify an extensive reservoir
of blood cells (hemocytes) at the respiratory epithelia (tracheal air sacs) of the
thorax and head. Lineage tracing and functional analyses demonstrate that the majority
of adult hemocytes are phagocytic macrophages (plasmatocytes) from the embryonic lineage
that parallels vertebrate tissue macrophages. Surprisingly, we find no sign of adult
hemocyte expansion. Instead, hemocytes play a role in relaying an innate immune response
to the blood cell reservoir: through Mid signaling and the Jak/Stat pathway ligand
Upd3, hemocytes act as sentinels of bacterial infection, inducing expression of the
antimicrobial peptide Drosocin in respiratory epithelia and colocalizing fat body
domains. Drosocin expression in turn promotes animal survival after infection. Our
work identifies a multisignal relay of organismal humoral immunity, establishing adult
Drosophila as model for inter-organ immunity.