CLN8 protein may be implicated in the endocellular translocation of cytolethal distending toxin produced by Campylobacter.

Campylobacter jejuni is one of the major causes of foodborne disease (Adzitey et al 2012), in humans worldwide causing mainly gastroenteric syndromes. Further than enteric pathology, the C. jejuni infection is one of the risk factors for the development of secondary sequela such as the Guillain–Barré syndrome (Shahrizaila et al 2021). The only exotoxin described as produced by the C. jejuni is referred to as cytolethal distending toxin (CDT) that fits the AB2 toxin model family of exotoxins, and its production strongly related with the symptoms of campylobacteriosis. The CDT comprised the binding subunits CTD-A and CTD-C and the active subunit is CTD-B and is released by microvesicles probably in conditions of strong environmental competitiveness. The acute consequences of campylobacteriosis have been attributed to the toxic activities of the CTD on mucosal cells. The released CDT can interact with host cell surface in the context of membrane lipid rafts binding the cholesterol “via” subunit A and C. The active CTD-B is internalized by the interaction with Cellugyrin (Synaptogyrin-2) translocated inside end-cellular vesicles and from cell membrane and according to recent literature data (Boesze-Battaglia et al 2024), this is a requisite role in the earliest stages of internalization from lipid rafts. CNL8 is a protein involved in a kind of storage lysosomal disease, indicated as ceroid neuronal lipofuscinosis (CNL; Lonka et al 2000). Homozygous mutations in CLN8 gene, located in the chromosome 8, lead to the development of progressive symptoms in the early stage of life that is characterized by psychomotor deterioration, visual failure, and premature death. The complete function of CLN8 in the contest of cell physiology is not fully comprised but was described as directly involved in the endo-cellular translocation of the lysosomal enzymes (Di Ronza et al. 2018). In recent paper the genetic of asymptomatic carriers of campylobacters was indagated in a large corte of middle east Asian population, in comparison with the symptomatic carriers (Munday R. M. et al 2022). The authors demonstrate a 2-fold lower risk of having a symptomatic campylobacteriosis in the subjects carrying different allele in the region on chromosome 8 in intron 4 of the rho guanine nucleotide exchange factor 10 gene (ARHGEF10) locus (SNP G>A). This SNP is also associated with decreased expression of the neighbouring CLN8 gene. The authors further, speculated that CLN8 could be involved in the intracellular translocation of CDT. By using a CRISPR approach, we have prepared a CLN8null cell line on which we compared the effect of C. jejuni ATCC29428 producing CDT bacterial lysates, in comparison with the parental line cell. The CLN8null cell respond differently to CDT treatment comparing distending effect, ATP content (cytotoxicity), Bcl2 response. These preliminary, few results are in line with the genomic data described in middle east Asian population, but further experiments have been carried out to validate the observed differences and the possible interaction between CLN8 and the CDT subunits. If these data are confirmed and improved by CLN8/CDT interaction experiments, there would be a better understanding of CTD diffusion in the lysosome, Golgi, and other endocellular target sites