Immune targets for schistosomiasis control identified by a genome-wide association study of East African snail vectors.

Autor:	Pennance T; College of Osteopathic Medicine of the Pacific - Northwest, Western University of Health Sciences, Lebanon, OR, USA., Tennessen JA; Harvard T.H. Chan School of Public Health, Boston, MA, USA., Spaan JM; College of Osteopathic Medicine of the Pacific - Northwest, Western University of Health Sciences, Lebanon, OR, USA., McQuistan T; College of Osteopathic Medicine of the Pacific - Northwest, Western University of Health Sciences, Lebanon, OR, USA., Ogara G; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Rawago F; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Andiego K; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Mulonga B; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Odhiambo M; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Mutuku MW; Centre for Biotechnology Research and Development, Kenya Medical Research Institute (KEMRI), P.O. Box 54840-00200, Nairobi, Kenya., Mkoji GM; Centre for Biotechnology Research and Development, Kenya Medical Research Institute (KEMRI), P.O. Box 54840-00200, Nairobi, Kenya., Loker ES; Department of Biology, Center for Evolutionary and Theoretical Immunology, Parasite Division Museum of Southwestern Biology, University of New Mexico, Albuquerque, New Mexico, USA., Odiere MR; Centre for Global Health Research, Kenya Medical Research Institute (KEMRI), P. O. Box 1578-40100, Kisumu, Kenya., Steinauer ML; College of Osteopathic Medicine of the Pacific - Northwest, Western University of Health Sciences, Lebanon, OR, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 02. Date of Electronic Publication: 2024 Sep 02.
DOI:	10.1101/2024.08.30.610565
Abstrakt:	Schistosomiasis, afflicting >260 million people worldwide, could be controlled by preventing infection of freshwater snail vectors. Intestinal schistosomiasis, caused by Schistosoma mansoni , occurs predominantly in Sub-Saharan Africa and is vectored by Biomphalaria sudanica and related Biomphalaria species. Despite their importance in transmission, very little genomic work has been initiated in African snails, thus hindering development of novel control strategies. To identify genetic factors influencing snail resistance to schistosomes, we performed a pooled genome-wide association study (pooled-GWAS) on the offspring of B. sudanica collected from a persistent hotspot of schistosomiasis in Lake Victoria, Kenya, and exposed to sympatric S. mansoni . Results of the pooled-GWAS were used to develop an amplicon panel to validate candidate loci by genotyping individual snails. This validation revealed two previously uncharacterized, evolutionarily dynamic regions, SudRes1 and SudRes2 , that were significantly associated with resistance. SudRes1 includes receptor-like protein tyrosine phosphatases and SudRes2 includes a class of leucine-rich repeat-containing G-protein coupled receptors, both comprising diverse extracellular binding domains, suggesting roles in pathogen recognition. No loci previously tied to schistosome resistance in other snail species showed any association with compatibility suggesting that loci involved in the resistance of African vectors differ from those of neotropical vectors. Beyond these two loci, snail ancestry was strongly correlated with schistosome compatibility, indicating the importance of population structure on transmission dynamics and infection risk. These results provide the first detail of the innate immune system of the major schistosome vector, B. sudanica , informing future studies aimed at predicting and manipulating vector competence. Competing Interests: Competing Interest Statement: The authors declare no competing interests
Databáze:	MEDLINE
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