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Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

Bataille A, Cashins SD, Grogan L, Skerratt LF, Hunter D, McFadden M, Scheele B, Brannelly LA, Macris A, Harlow PS, Bell S, Berger L, Waldman B - Proc. Biol. Sci. (2015)

Bottom Line: We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove.Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd.The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.

ABSTRACT
The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.

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Association of the MHC class II β1 domain with survival to Bdin L. v. alpina. (a) Frequency ofMHC class II β1 alleles (Livea) in subjectsthat survived (red) and succumbed (blue) to experimental infectionby Bd, indicating alleles encoding the P9 and P6 pocket compositionsmost frequent in Bd-resistant amphibians; frequency of individualswith two (2/2), one (1/2) or no (0/2) MHC-II β1 alleles withthe specific P9 residue composition. (b) Survivalcurves for individuals during the course of the Bd infectionexperiment with respect to the presence of the specific P9 pocketresidue composition in two (2/2), one (1/2) or none (0/2) of theirtwo MHC-II β1 domains.
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RSPB20143127F3: Association of the MHC class II β1 domain with survival to Bdin L. v. alpina. (a) Frequency ofMHC class II β1 alleles (Livea) in subjectsthat survived (red) and succumbed (blue) to experimental infectionby Bd, indicating alleles encoding the P9 and P6 pocket compositionsmost frequent in Bd-resistant amphibians; frequency of individualswith two (2/2), one (1/2) or no (0/2) MHC-II β1 alleles withthe specific P9 residue composition. (b) Survivalcurves for individuals during the course of the Bd infectionexperiment with respect to the presence of the specific P9 pocketresidue composition in two (2/2), one (1/2) or none (0/2) of theirtwo MHC-II β1 domains.

Mentions: We genotyped the β1 domain of one MHC-II locus in 84 individuals,including the six survivors, that we had inoculated with Bd. Twenty-two MHC-IIβ1 alleles were recovered, with eight alleles identified among thesurviving individuals (Livea-1, 2, 3b, 5a, 5b, 11, 13 and 14;figure 3; electronicsupplementary material, table S6 and figure S1). These eight alleles hadidentical residues at five codon positions associated with the P9 pocket,corresponding to the composition identified in resistant amphibians worldwide(table 1 and figure 1; electronicsupplementary material, S1). Subjects that died had significantly lowerfrequencies of alleles with the specific P9 pocket composition than those thatsurvived (, p = 0.004; table 1 and figure 3). None of the eightalleles had the P4 pocket composition identified in the worldwide MHC-IIβ1 alignment, and only two alleles had the targeted P6 pocket composition(table 1). We identifiedanother 15 alleles in individuals that did not survive infection. Six of thesealleles presented the P9 pocket composition identified in Bd-resistantamphibians (figures 1 and 3; electronic supplementarymaterial, S1). Figure 3.


Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

Bataille A, Cashins SD, Grogan L, Skerratt LF, Hunter D, McFadden M, Scheele B, Brannelly LA, Macris A, Harlow PS, Bell S, Berger L, Waldman B - Proc. Biol. Sci. (2015)

Association of the MHC class II β1 domain with survival to Bdin L. v. alpina. (a) Frequency ofMHC class II β1 alleles (Livea) in subjectsthat survived (red) and succumbed (blue) to experimental infectionby Bd, indicating alleles encoding the P9 and P6 pocket compositionsmost frequent in Bd-resistant amphibians; frequency of individualswith two (2/2), one (1/2) or no (0/2) MHC-II β1 alleles withthe specific P9 residue composition. (b) Survivalcurves for individuals during the course of the Bd infectionexperiment with respect to the presence of the specific P9 pocketresidue composition in two (2/2), one (1/2) or none (0/2) of theirtwo MHC-II β1 domains.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389617&req=5

RSPB20143127F3: Association of the MHC class II β1 domain with survival to Bdin L. v. alpina. (a) Frequency ofMHC class II β1 alleles (Livea) in subjectsthat survived (red) and succumbed (blue) to experimental infectionby Bd, indicating alleles encoding the P9 and P6 pocket compositionsmost frequent in Bd-resistant amphibians; frequency of individualswith two (2/2), one (1/2) or no (0/2) MHC-II β1 alleles withthe specific P9 residue composition. (b) Survivalcurves for individuals during the course of the Bd infectionexperiment with respect to the presence of the specific P9 pocketresidue composition in two (2/2), one (1/2) or none (0/2) of theirtwo MHC-II β1 domains.
Mentions: We genotyped the β1 domain of one MHC-II locus in 84 individuals,including the six survivors, that we had inoculated with Bd. Twenty-two MHC-IIβ1 alleles were recovered, with eight alleles identified among thesurviving individuals (Livea-1, 2, 3b, 5a, 5b, 11, 13 and 14;figure 3; electronicsupplementary material, table S6 and figure S1). These eight alleles hadidentical residues at five codon positions associated with the P9 pocket,corresponding to the composition identified in resistant amphibians worldwide(table 1 and figure 1; electronicsupplementary material, S1). Subjects that died had significantly lowerfrequencies of alleles with the specific P9 pocket composition than those thatsurvived (, p = 0.004; table 1 and figure 3). None of the eightalleles had the P4 pocket composition identified in the worldwide MHC-IIβ1 alignment, and only two alleles had the targeted P6 pocket composition(table 1). We identifiedanother 15 alleles in individuals that did not survive infection. Six of thesealleles presented the P9 pocket composition identified in Bd-resistantamphibians (figures 1 and 3; electronic supplementarymaterial, S1). Figure 3.

Bottom Line: We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove.Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd.The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.

ABSTRACT
The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.

Show MeSH
Related in: MedlinePlus