Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7
(A) F40F4.6 RNAi significantly shortened the lifespan of irg-7(zc6) mutants (Mantel-Cox, P<0.0001) but did not affect the lifespan of otherwise wild-type animals (Mantel-Cox,P = 0.9). Mean lifespans are indicated within each graph. See S2 Table for more lifespan data. (B) Representative fluorescence micrographs (100-fold magnification) of day-1 adults harboring an integrated Phsp-4::gfp transgene. F40F4.6 RNAi significantly reduced the expression of the Phsp-4::gfp in zc6 mutants. Asterisks mark Student's T-test values of P<0.001 compared to fluorescence on control RNAi. 40 animals were analyzed per genotype. Error bars represent SE of 3 independent biological replicates. (C) Expression of fosmid WRM0619aB08 (which includes F40F4.6) significantly extended the lifespan of wild-type animals (Mantel-Cox, P<0.001), whereas expression of the partially overlapping fosmid WRM0635bF05 (which does not include F40F4.6) did not extend the lifespan of wild-type animals (Mantel-Cox, P = 0.4). Mean lifespans are indicated within each graph. See S2 Table for more lifespan data. (D) Expression of an NLS-RFP reporter fused to the putative promoter upstream of the F40F4.6 gene drives expression in the posterior cells of the intestine. Fluorescence of this reporter increased upon exposure of L4 animals to Photorhabdus luminescens subsp Hb bacteria (HB) or Enterococcus faecalis bacteria (EF). Asterisks mark Student's T-test values of P<0.001 compared to wild-type fluorescence on OP50 bacteria. (E) Schematic representation of the major domains in the F40F4.6 protein. The region deleted by the zc6 mutation is indicated by a dashed line. This region includes an EGF domain. Note that the deletion preserves the ORF of the original gene. See S2 Fig for sequence data.