Abstract
Pathogenic bacterial infection imposes considerable cellular stress on the host and often leads to attenuation of mRNA translation. In this translation-suppressive environment, it is unclear how the host synthesizes various antimicrobial peptides (AMPs) to mount innate immune response. Here, we use
Drosophila
as a model to demonstrate that AMP production during infection relies on a translation bias mechanism mediated by the inhibitor of cap-dependent translation 4E-BP (
Drosophila
Thor), and the AMP 5′ UTRs that can undergo cap-independent translation. We found that 4E-BP is induced upon infection with the pathogenic bacteria
Ecc15
by the stress-responsive transcription factor ATF4, and its upstream kinase GCN2. Moreover, loss of
gcn2
,
atf4
or
4e-bp
compromised immunity against
Ecc15
. In 4E-BP mutants, the transcriptional induction of AMPs after infection was unaffected, while the protein levels of AMPs were substantially reduced in their hemolymph. Analysis of the 5′ UTRs of AMPs using cell-based bicistronic reporters and
in vitro
translation analysis indicated that AMPs are translated in a cap-independent mechanism. Analysis of bicistronic reporters in the presence of 4E-BP indicate that infection enhances cap-independent translational activity associated with AMP 5′ UTRs, accounting for enhanced AMP translation during infection.