The Landscape of Human Genes Involved in the Immune Response to Parasitic Worms

Overview

Journal BMC Evol Biol

Publisher Biomed Central

Specialty Biology

Date 2010 Sep 3

PMID 20807397

Citations 27

Authors

Matteo Fumagalli

Uberto Pozzoli

Rachele Cagliani

Giacomo P Comi

Nereo Bresolin

Mario Clerici

Manuela Sironi

Affiliations

Soon will be listed here.

Abstract

Background: More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure.

Results: Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections.

Conclusions: Our data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans.

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