Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans

Abstract

When an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.

Decomposing variation in immune response in a wild rodent population

“…They included, for example, markers involved in the insulin signalling pathway. This is in line with previous studies, which suggest that insulin plays a key role in coordinating an organism’s response to infection, influencing, in particular, the allocation of resources 33,34 . One of these markers, Pdk1 , was also among the top convergent markers.…”

Evolutionary plasticity in the innate immune function of Akirin

“…Ratio of green fluorescence (GFP) to size (TOF) in wild-type (IG274) or ceh-18 ( mg57 ) mutant (IG1714) worms carrying frIs7 , infected or not with D . coniospora for 16 h (yellow and blue, respectively; data for IG274 is as Fig 3B in [ 53 ]), and IG274 worms treated with RNAi against sta-1 (control) or ceh-18 and, from left to right, exposed to high salt (purple; cpsf-2(RNAi) is a positive control, sta-2(RNAi) a negative control [ 11 ]), in worms also expressing GPA-12* in the epidermis, and in the rde-1 ( ne219 ); wrt-2p :: RDE-1 background and infected by D . coniospora .…”

“…The strains IG274 (containing frIs 7[ nlp-29p :: gfp , col-12p :: DsRed ] IV ) and IG1389 (containing frIs7 and frIs30 [ col-19p :: GPA-12* , unc-53pB :: gfp ] I ) have been described elsewhere [ 13 , 38 ]. We recently validated the use of strains carrying col-19p :: GPA-12* as a model for the inductive part of the epidermal innate immune response [ 53 ].…”

Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria

“…Thus, the OST complex may modulate immune responses by regulating the post-translational modification, intracellular trafficking, and/or secretion of immune effector proteins such as anti-microbial peptides, cytokines, and receptor proteins. VIT-6 is secreted by intestinal cells and transported into oocytes for lipid transfer from parents to offspring [38,39,[54][55][56]. Our data suggest that OST mediates N-glycosylation of VIT-6 to maintain defense against PA14 infection.…”