Negative relationships between cellular immune response, Mhc class II heterozygosity and secondary sexual trait in the montane water vole Nathalie Charbonnel, Josef Bryja, Maxime Galan, Julie Deter, Charlotte Tollenaere, Yannick Chaval, Serge Morand, Jean-Francois Cosson To cite this version: Nathalie Charbonnel, Josef Bryja, Maxime Galan, Julie Deter, Charlotte Tollenaere, et al.. Nega- tive relationships between cellular immune response, Mhc class II heterozygosity and secondary sex- ual trait in the montane water vole. Evolutionary Applications, Blackwell, 2010, 3 (3), pp.279-290. 10.1111/j.1752-4571.2009.00108.x. hal-01219022 HAL Id: hal-01219022 https://hal.archives-ouvertes.fr/hal-01219022 Submitted on 21 Oct 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NonCommercial| 4.0 International License Evolutionary Applications ISSN 1752-4571 ORIGINAL ARTICLE Negative relationships between cellular immune response, Mhc class II heterozygosity and secondary sexual trait in the montane water vole Nathalie Charbonnel,1 Josef Bryja,1,2 Maxime Galan,1 Julie Deter,3 Charlotte Tollenaere,1 Yannick Chaval,1 Serge Morand4 and Jean-Franc¸ois Cosson1 1 Centre de Biologie et Gestion des Populations UMR (INRA/IRD/Cirad/Montpellier SupAgro), INRA-EFPA, Montferrier sur Lez Cedex, France 2 Department of Population Biology, Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Studenec, Czech Republic 3 IFREMER, De´ partement Environnement, Microbiologie et Phycotoxines, Laboratoire de Microbiologie, ZI de la pointe du diable, Plouzane´ , France 4 Universite´ Montpellier II, CNRS, Institut des Sciences de l’Evolution de Montpellier, Montpellier Cedex, France Keywords Abstract abundance cycles, Dqa and Drb, immunocompetence handicap, Mhc class II Heterogeneities in immune responsiveness may affect key epidemiological genes, parasite-mediated balancing selection, parameters and the dynamics of pathogens. The roles of immunogenetics in sexual selection. these variations remain poorly explored. We analysed the influence of Major histocompatibility complex (Mhc) genes and epigamic traits on the response to Correspondence phytohaemagglutinin in males from cyclic populations of the montane water Nathalie Charbonnel, Centre de Biologie et vole (Arvicola scherman). Besides, we tested the relevance of lateral scent glands Gestion des Populations UMR (INRA/IRD/Cirad/ Montpellier SupAgro), INRA-EFPA, Campus as honest signals of male quality. Our results did not corroborate neither the International de Baillarguet, CS 30016, 34988 hypotheses of genome-wide heterozygosity-fitness correlation nor the Mhc het- Montferrier sur Lez Cedex, France. erozygote advantage. We found a negative relationship between Mhc hetetozyg- Tel.: +33 (0)4 99 62 33 02; osity and response to phytohaemagglutinin, mediated by a specific Mhc fax: +33 (0)4 99 62 33 45; homozygous genotype. Our results therefore support the hypothesis of the e-mail: [email protected] Arte-Dqa-05 homozygous genotype being a ‘good’ Mhc variant in terms of immunogenetic quality. The development of the scent glands seems to be an Received: 30 October 2009 Accepted: 10 November 2009 honest signal for mate choice as it is negatively correlated with helminth load. First published online: 25 January 2010 The ‘good gene’ hypothesis was not validated as Arte-Dqa-05 homozygous males did not exhibit larger glands. Besides, the negative relationship observed doi:10.1111/j.1752-4571.2009.00108.x between the size of these glands and the response to phytohaemagglutinin, mainly for Mhc homozygotes, corroborates the immunocompetence handicap hypothesis. The Mhc variants associated with larger glands remain yet to be determined. influence key epidemiological parameters such as parasite Introduction intensity, transmission or virulence (e.g. Dowel 2001). Since the 1990s, ecological immunology has addressed the Proximal factors influencing variation in immune physiological and molecular bases of variations in defences are multiple, including physiological or environ- immune responsiveness by placing immunity in the con- mental factors. They have been largely investigated (for text of ecology and adaptation (Schulenburg et al. 2009). rodents, see Nelson et al. 2002). Besides, the influence of Understanding these disparities across individuals or spe- genetics on the intensity of the immune response still cies has major implications in evolutionary ecology as remains scarcely explored in natural populations. Major immunocompetence probably represents one of the main histocompatibility complex (Mhc) genes are relevant can- components of fitness (Lochmiller and Deerenberg 2000). didates to address this question. They encode for glyco- These variations are also important for zoonosis epidemi- proteins that recognize antigens, bind peptides derived ology. Heterogeneity in host susceptibility may strongly from them and present them to lymphocyte T cells (Klein ª 2010 Blackwell Publishing Ltd 3 (2010) 279–290 279 Immunity and genetics in A. scherman populations Charbonnel et al. 1986). Therefore, they participate in the initiation of the and Hill 2004; Neff and Pitcher 2005). Males bearing antigen-specific immune response by inducing communi- ‘good’ alleles, i.e. alleles that increase individual fitness cation among different cellular components of the (Andersson 1994) by conferring higher immunocompe- immune system (Klein 1986). In particular, antigen pre- tence for example, should be preferred. Benefits of such sentation via Mhc class II molecules plays a key role in mating are multiple and include direct advantages, i.e. the initiating and maintaining cell-mediated and humoral avoidance of parasitized individuals, as well as indirect immune responses. ones, i.e. the transmission of these ‘good alleles’ to off- Few empirical studies have provided evidence for the springs (Hamilton and Zuk 1982). Under this scenario, role of Mhc gene polymorphism in the control of differ- we might expect females to seek mates carrying specific ences in immune responsiveness (e.g. Makhatadze et al. Mhc alleles, locally adapted against prevalent pathogens 1995; Apanius et al. 1997; Zhou and Lamont 2003; Kurtz or associated with higher immune responses. Assuming et al. 2004). In natural populations, the role of Mhc that mates homozygous for such ‘good’ alleles would be alleles was investigated rather than that of Mhc heterozy- even more favoured (e.g. in Salmo salar, Langefors et al. gosity (but see Kurtz et al. 2004 for laboratory experi- 2001), we would expect a negative relationship between ments; Makhatadze et al. 1995 for human studies). It was Mhc gene heterozygosity and the intensity of immune thus worthy to assess the effects of Mhc gene heterozygos- response. This relationship would hence only be driven ity on immunocompetence. From a theoretical point of by those particular ‘good’ Mhc alleles. view, Doherty and Zinkernagel (1975) suggested that Mhc Next, studying the relationships between the develop- heterozygotes should exhibit the highest immunocompe- ment of a secondary sexual character and immune tence (the ‘heterozygote advantage’ HA hypothesis), in responses might provide complementary insights into the terms of the recognition and elimination of pathogens, mechanisms driving these associations between Mhc gene because such individuals could present a broader range of and immune response. pathogen-derived peptides. Then empirical works rather On one hand, a negative relationship between a second- focused on the associations between Mhc heterozygosity ary sexual trait and immune responses would support the and resistance/tolerance to one or multiple parasites than immunocompetence handicap hypothesis (ICHH; Folstad on associations between Mhc heterozygosity and immune and Karter 1992; Wedekind and Folstad 1994). The ICHH responsiveness (e.g. Froeschke and Sommer 2005; de Eyto postulates that only males carrying genetic characteristics et al. 2007; Oliver et al. 2009). associated with superior immunocompetence/better disease Different patterns of relationships between Mhc gene resistance might afford to allocate more resources to costly heterozygosity and the intensity of immune response ornament traits at the expense of the immune function might be observed. (Hamilton and Zuk 1982; Folstad and Karter 1992; Wede- On one hand, positive associations are expected under kind and Folstad 1994). This hypothesis relies on Zahavi’s the models of genome-wide heterozygosity-fitness correla- handicap theory, which proposes that individuals that tion (HFC) or Mhc heterozygote advantage (HA, Doherty express male epigamic traits are handicapped by a reduced and Zinkernagel 1975). Under the HFC hypothesis, positive immune response (Zahavi 1975). In vertebrates, this handi- associations between heterozygosity estimated at neutral cap is linked to testosterone, the primary male sex hor- markers and the intensity of immune response should also mone, which is required for the