Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity

Thou has been identified as a new type of gene involved in Drosophila host immune defense. Thor is a member of the 4E-binding protein (4E-BP) family, which in mammals has been defined as critical regulators in a pathway that controls initiation of translation through binding eukaryotic initiation fa ctor 4E (eIF4E), Without an infection, Thor is expressed during all develop mental stages and transcripts localize to a wide variety of tissues, includ ing the reproductive system. In response to bacterial infection and, to a l esser extent, by wounding, Thor is up-regulated. The Thor promoter has the canonical NF kappa B and associated GATA recognition sequences that have be en shown to be essential for immune induction, as well as other sequences c ommonly found for Drosophila immune response genes, including interferon-re lated regulatory sequences, In survival tests, Thor mutants show symptoms o f being immune compromised, indicating that Thor may be critical in host de fense. In contrast to Thor, Drosophila eIF4E is not induced by bacterial in fection. These findings for Thor provide the first evidence that a 4E-BP fa mily member has a role in immune induction in any organism. Further, no gen e in the translation initiation pathway that includes 4E-BP has been previo usly found to be immune induced. Our results suggest either a role for tran slational regulation in humoral immunity or a new, nontranslational functio n for 4E-BP type genes.