genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population遗传多样性在与免疫相关细胞因子的变异和耐多种病原体人口自然啮齿动物.pdfVIP

Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population 1 1 1,2 3 1 Andrew K. Turner *, Mike Begon , Joseph A. Jackson , Janette E. Bradley , Steve Paterson 1 Institute of Integrative Biology, Biosciences Building, University of Liverpool, Liverpool, United Kingdom, 2 Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth, United Kingdom, 3 School of Biology, University of Nottingham, Nottingham, United Kingdom Abstract Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleu