Investigating the immune function of the Drosophila melanogaster MACPF protein Torso-like (#326)
Membrane attack
complex/perforin-like (MACPF) proteins perform key roles in vertebrate innate
immunity. Torso-like (Tsl) is the only known MACPF protein in Drosophila melanogaster, discovered for
its developmental role in terminal patterning of the embryo. We have discovered
an additional role for Tsl in the Drosophila
immune response. Well established immune response assays were conducted by infecting
a tsl null mutant with various strains of bacteria and observing survival
post-infection. We have shown that tsl
null mutants have a defective immune response to gram-positive, but not
gram negative bacteria. This is extremely unexpected, since the mammalian
membrane attack complex targets gram-negative bacteria through disruption of
the outer bacterial membrane. Gram-positive bacterial cell walls have a
different composition and upon infection are detected by distinct Drosophila
pattern recognition proteins. It therefore seems likely that tsl performs a different role in the fly immune system
than that of vertebrate MACPF proteins involved in immune defence. This result is
suggestive of a role for Tsl in the Toll signalling pathway, however further
experiments showed that tsl null mutants can successfully induce
transcriptional targets of the pathway. Ongoing experiments are testing whether tsl functions in cellular immunity, acting to assist
the phagocytosis of pathogens. It is also of interest to investigate if Tsl
interacts with the same genetic pathway(s) or partner proteins as it does in
development to determine the similarities and/or differences in Tsl function between
these processes.