Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates

BACKGROUND: Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4) plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs) in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae), from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success. RESULTS: Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected. CONCLUSIONS: Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better understanding of the actual components of the immune response that mediate protection against gastro-intestinal parasites.