Previous and recent investigations on the innate immune response of Drosophila have identified certain mechanisms that promote pathogen elimination. However, the function of Thioester-containing proteins (TEPs) in the fly still remains elusive. Recently we have shown the contribution of TEP4 in the antibacterial immune defense of Drosophila against non-pathogenic E. coli, and the pathogens Photorhabdus luminescens and P. asymbiotica. Here we studied the function of Tep genes in both humoral and cellular immunity upon E. coli and Photorhabdus infection. We found that while Tep2 is induced after Photorhabdus and E. coli infection; Tep6 is induced by P. asymbiotica only. Moreover, functional ablation of hemocytes results in significantly low transcript levels of Tep2 and Tep6 in response to Photorhabdus. We show that Tep2 and Tep6 loss-of-function mutants have prolonged survival against P. asymbiotica, Tep6 mutants survive better the infection of P. luminescens, and both tep mutants are resistant to E. coli and Photorhabdus. We also find a distinct pattern of immune signaling pathway induction in E. coli or Photorhabdus infected Tep2 and Tep6 mutants. We further show that Tep2 and Tep6 participate in the activation of hemocytes in Drosophila responding to Photorhabdus. Finally, inactivation of Tep2 or Tep6 affects phagocytosis and melanization in flies infected with Photorhabdus. Our results indicate that distinct Tep genes might be involved in different yet crucial functions in the Drosophila antibacterial immune response.

is an outstanding model for studying host antipathogen defense. Although substantial progress has been made in understanding how metabolism and immunity are interrelated in flies, little information has been obtained on the molecular players that regulate metabolism and inflammation in during pathogenic infection. Recently, we reported that the inactivation of thioester-containing protein 2 () and promotes survival and decreases the bacterial burden in flies upon infection with the virulent pathogens and Here, we investigated physiological and pathological defects in mutant flies in response to challenge. We find that and loss-of-function mutant flies contain increased levels of carbohydrates and triglycerides in the presence or absence of infection. We also report that infection leads to higher levels of nitric oxide and reduced transcript levels of the apical caspase-encoding gene in and mutants. We show that and are upregulated mainly in the fat body rather than the gut in -infected wild-type flies and that mutants contain decreased numbers of bacteria in both tissue types. We propose that the inactivation of or in adult flies results in lower levels of inflammation and increased energy reserves in response to , which could confer a survival-protective effect during the initial hours of infection.