Innate immunity in C. elegans

Abstract

In its natural habitat, C. elegans encounters a wide variety of microbes, including food, commensals and pathogens. To be able to survive long enough to reproduce, C. elegans has developed a complex array of responses to pathogens. These activities are coordinated on scales that range from individual organelles to the entire organism. Often, the response is triggered within cells, by detection of infection-induced damage, mainly in the intestine or epidermis. C. elegans has, however, a capacity for cell non-autonomous regulation of these responses. This frequently involves the nervous system, integrating pathogen recognition, altering host biology and governing avoidance behaviour. Although there are significant differences with the immune system of mammals, some mechanisms used to limit pathogenesis show remarkable phylogenetic conservation. The past twenty years have witnessed an explosion of host-pathogen interaction studies using C. elegans as a model. This review will discuss the broad themes that have emerged and highlight areas that remain to be fully explored. Natural environment and microbiotaCaenorhabditis elegans is a small free-living nematode found worldwide, predominately in humid, temperate areas where it can feed on the bacteria that proliferate on decaying vegetation (Schulenburg and Félix, 2017). Its natural environment comprises a complex community of microbes, including bacteria, fungi and viruses, including many parasitic species. The effect of environmental microbes on worm fitness can be beneficial, detrimental or mixed (Khan et al., 2018). And as the same microorganism can sometime be either beneficial or detrimental depending on the environmental conditions or the genotype of the host (Gravato-Nobre et al., 2020;Zarate-Potes et al., 2020), we will use the terms of "pathogen" or "commensal" for a given microbe as a simplification.A broad range of microorganisms can infect nematodes in a variety of ways. Different fungi, for example, have independently acquired the capacity to infect worms using diverse strategies (Lebrigand et al., 2016). Some species capture their prey with adhesive structure such as Arthobotrys oligosora or elegant mechanical traps like the constricting rings of al., 2001). Apart from recognition of viral replication products by DRH-1/RIG-1 (Ashe et al., 2013), see below, examples of direct microbial detection that lead to immune pathway activation remain elusive in C. elegans (Kim and Ewbank, 2018).Various molecules from the host, such as the protein HMGB1, formylated peptides, mitochondrial DNA, or uric acid, amongst many others, can also trigger innate immune activity (Tang et al., 2012). Matzinger and colleagues recognized that cells are agnostic with regard to the origin of the damage signals and will respond to them regardless of the preceding event, which led to the 'damage-associated molecular pattern' or DAMP hypothesis (Matzinger, 2002;Seong and Matzinger, 2004). On this basis, the field of innate immunity widened to include recognition of both non-self and se...

Meisosomes, folded membrane platforms, link the epidermis to the cuticle inC. elegans

“…If the pathway leading to AMP induction in the epidermis is well described (reviewed in (Kim and Ewbank, 2018; Martineau et al, 2021)), exactly how the epidermis senses cuticular damage remains obscure. Part of the induction seen in dpy-10 mutants is the consequence of an increase in the levels of hydroxyphenyllactic acid (HPLA).…”

C. elegans: out on an evolutionary limb

“…There have been many reviews of the field in the last couple of years (e.g. Garcia-Sanchez et al 2021;Harding and Ewbank 2021;Kim and Flavell 2020;Martineau et al 2021;Miles et al 2019;Penkov et al 2019;Radeke and Herman 2021;Singh and Aballay 2020;Wani et al 2020;Willis et al 2021), and we will not attempt to be exhaustive here. Rather we will mainly take an evolutionary perspective to examine in what ways innate immunity in C. elegans resembles that of other animals and in what ways it differs.…”

Box C/D small nucleolar ribonucleoproteins regulate mitochondrial surveillance and innate immunity

“…Interestingly, the loss of box C/D snoRNPs increased survival of atf-7(gk715) and pmk-1(km25) mutants, as was observed for wild-type worms ( Figs 8D and S9 and S4 Table ). These results were not entirely unexpected, considering that there are multiple immune pathways in the host and some innate immune genes are outside of the control of the MAPK pathway [ 67 , 68 ]. Together, these results strengthen our hypothesis that the loss of box C/D snoRNPs increased host immune responses.…”