The distinct function of Tep2 and Tep6 in the immune defense of Drosophila melanogaster against the pathogen Photorhabdus

Abstract

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.

Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization

“…The deletion of four Drosophila Teps did not render the flies susceptible to infection with non-pathogenic Gram-negative bacteria [55]. Tep2 has been reported to be required for the uptake of E. coli, a Gram-negative bacterium, by cultured S2 cells [48], a finding confirmed in vivo [49]. In contrast, we find no involvement of Tep2 in our in vivo intestinal infection model with P. aeruginosa, at least in terms of virulence, but do detect a requirement for Tep4 in phagocytosis and opsonization assays.…”

“…The expression patterns of Tep1‐4 have been documented by in situ hybridization . The exact function of each Tep in host defense remains poorly understood despite several studies and their potential role as opsonins has not been definitely determined . Although an initial study failed to reveal a role of Tep1 , Tep2 , Tep3 , or Tep4 in several infection models, even when Tep2‐Tep3‐Tep4 triple mutants were assayed , a quadruple Tep1‐Tep2‐Tep3‐Tep4 mutant was reported to be sensitive to some fungal and Gram‐positive bacterial infections, likely because Toll pathway activation is impaired in this quadruple mutant .…”

“…Although an initial study failed to reveal a role of Tep1 , Tep2 , Tep3 , or Tep4 in several infection models, even when Tep2‐Tep3‐Tep4 triple mutants were assayed , a quadruple Tep1‐Tep2‐Tep3‐Tep4 mutant was reported to be sensitive to some fungal and Gram‐positive bacterial infections, likely because Toll pathway activation is impaired in this quadruple mutant . In addition to this apparent redundancy in function, different Tep genes may also have pathogen‐specific functions: Whereas Tep2 mutant or Tep4 mutant was reported to be more sensitive to infections with Porphyromonas gingivalis , they unexpectedly were more resistant to challenge with Photorhabdus species .…”

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

“…Substantial information on the function of TEPs in Anopheles mosquitoes has been acquired, but only a few studies have examined the contribution of TEPs to the antimicrobial immune response of Drosophila (11,(29)(30)(31)(32)(33)(34). Recently, we reported that Tep2, Tep4, and Tep6 in Drosophila are transcriptionally upregulated after infection with Photorhabdus luminescens or Photorhabdus asymbiotica (11,35,36). In particular, the inactivation of Tep2, Tep4, and Tep6 in Drosophila prolongs the survival of the mutants in response to Photorhabdus infection, which is accompanied by a lower level of persistence of the pathogens in infected flies.…”

Thioester‐containing proteins in the tsetse fly (Glossina) and their response to trypanosome infection

“…Of note is the significant up‐regulation of Gmm_TEP4 (MCR), especially in the salivary glands, of T. brucei ‐infected flies. In D. melanogaster , the MCR has been shown to have multiple roles in innate immunity (Stroschein‐Stevenson et al ., ; Shokal et al ., ) and in the formation and maintenance of the septate junctions (Batz et al ., ; Hall et al ., ). In T. brucei ‐infected salivary glands, the parasites tightly attach with their flagellum to the epithelial lining (Vickerman et al ., ), thereby possibly damaging the septate junctions.…”