Research article

The landscape of human genes involved in the immune response to parasitic worms

Matteo Fumagalli^1,2†, Uberto Pozzoli^1†, Rachele Cagliani¹, Giacomo P Comi³, Nereo Bresolin^1,3, Mario Clerici^4,5 and Manuela Sironi^1*

• * Corresponding author: Manuela Sironi manuela.sironi@bp.lnf.it

• † Equal contributors

Author Affiliations

¹ Scientific Institute IRCCS E. Medea, Bioinformatic Lab, Via don L. Monza 20, 23842 Bosisio Parini (LC), Italy

² Bioengineering Department, Politecnico di Milano, P.zza L. da Vinci, 32, 20133 Milan, Italy

³ Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Via F. Sforza 35, 20100 Milan, Italy

⁴ Department of Biomedical Sciences and Technologies LITA Segrate, University of Milan, Via F.lli Cervi 93, 20090 Milan, Italy

⁵ Don C. Gnocchi ONLUS Foundation IRCCS, Via Capecelatro 66, 20148 Milan, Italy

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BMC Evolutionary Biology 2010, 10:264 doi:10.1186/1471-2148-10-264

Published: 31 August 2010

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.