Structure and IgE Cross-Reactivity among Cashew, Pistachio, Walnut, and Peanut Vicilin-Buried Peptides.

Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.

Host Sex Modulates the Energetics of Pathogen Proliferation and Its Dependence on Environmental Resources.

AbstractSex differences in immunity are predicted to underlie much of the frequently observed sex differences in the prevalence or severity of infection. We propose the additional hypothesis that differences in the ability of males and females to acquire and use resources will also affect how readily a pathogen can convert host energy into transmission stages, thereby contributing to sex differences in infection dynamics. To test this we manipulated the resource environment of male and female Daphnia magna by altering the availability of food and then exposed hosts to a bacterial pathogen. We measured the production of transmission spores and virulence via the reduction in life span, together with feeding rates and changes in mass-independent metabolic rate, as a measure of the intake and expenditure of energy during infection. When raised in the presence of high resource levels, females more readily allowed for resources in the environment to be translated to pathogen exploitation, as represented by increased spore production, greater virulence, and higher energy use. In contrast, the traits of infected males were robust to changes in resource availability. High food availability thus exaggerated the degree of sexual dimorphism observed between the sexes. It also modified the relationship between host energy use, virulence, and pathogen spore production for each sex. These results suggest that a host's resource environment can affect how a male or female is exploited by a pathogen and may thus be an additional factor driving sex-specific patterns of disease susceptibility or severity.

Structure, Immunogenicity, and IgE Cross-Reactivity among Walnut and Peanut Vicilin-Buried Peptides.

Vicilin-buried peptides (VBPs) from edible plants are derived from the N-terminal leader sequences (LSs) of seed storage proteins. VBPs are defined by a common α-hairpin fold mediated by conserved CxxxCx(10-14)CxxxC motifs. Here, peanut and walnut VBPs were characterized as potential mediators of both peanut/walnut allergenicity and cross-reactivity despite their low (∼17%) sequence identity. The structures of one peanut (AH1.1) and 3 walnut (JR2.1, JR2.2, JR2.3) VBPs were solved using solution NMR, revealing similar α-hairpin structures stabilized by disulfide bonds with high levels of surface similarity. Peptide microarrays identified several peptide sequences primarily on AH1.1 and JR2.1, which were recognized by peanut-, walnut-, and dual-allergic patient IgE, establishing these peanut and walnut VBPs as potential mediators of allergenicity and cross-reactivity. JR2.2 and JR2.3 displayed extreme resilience against endosomal digestion, potentially hindering epitope generation and likely contributing to their reduced allergic potential.

Epitopes with similar physicochemical properties contribute to cross reactivity between peanut and tree nuts.

Many individuals with peanut (PN) allergy have severe reactions to tree nuts (TN) such as walnuts or cashews. Although allergenic proteins in TN and PN have overall low identity, they share discrete sequences similar in physicochemical properties (PCP) to known IgE epitopes. Here, PCP-consensus peptides (cp, 13 aa and 31 aa) were identified from an alignment of epitope rich regions of walnut vicilin, Jug r 2, leader sequence (J2LS) and cross-reactive epitopes in the 2S albumins of peanut and synthesized. A peptide similarity search in the Structural Database of Allergenic Proteins (SDAP) revealed a network of peptides similar (low property distance, PD) to the 13 aa cp (13cp) in many different plant allergens. Peptides similar to the 13cp in PN and TN allergens bound IgE from sera of patients allergic to PN and TN in peptide microarray analysis. The 13cp was used to produce a rabbit consensus peptide antibody (cpAB) that detected proteins containing repeats similar to the 13cp in western blots of various nut extracts, in which reactive proteins were identified by mass spectrometry. The cpAB bound more specifically to allergens and nut extracts containing multiple repeats similar to the 13 cp, such as almond (Pru du 6), peanut (Ara h 2) and walnut (Jug r 2). IgE binding to various nut extracts is inhibited by recombinant J2LS sequence and synthetic 31cp. Thus, several repeated sequences similar to the 13cp are bound by IgE. Multiple similar repeats in several allergens could account for reaction severity and clinically relevant cross-reactivity to PN and TN. These findings may help improve detection, diagnostic, and therapeutic tools.

Host sexual dimorphism affects the outcome of within-host pathogen competition.

Natural infections often consist of multiple pathogens of the same or different species. When coinfections occur, pathogens compete for access to host resources and fitness is determined by how well a pathogen can reproduce compared to its competitors. Yet not all hosts provide the same resource pool. Males and females, in particular, commonly vary in both their acquisition of resources and investment in immunity, but their ability to modify any competition between different pathogens remains unknown. Using the Daphnia magna-Pasteuria ramosa model system, we exposed male and female hosts to either a single genotype infection or coinfections consisting of two pathogen genotypes of varying levels of virulence. We found that coinfections within females favored the transmission of the more virulent pathogen genotype, whereas coinfections within male hosts resulted in equal transmission of competing pathogen genotypes. This contrast became less pronounced when the least virulent pathogen was able to establish an infection first, suggesting that the influence of host sex is shaped by priority effects. We suggest that sex is a form of host heterogeneity that may influence the evolution of virulence within coinfection contexts and that one sex may be a reservoir for pathogen genetic diversity in nature.

Erratum: The impact of host sex on the outcome of co-infection.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

The impact of host sex on the outcome of co-infection.

Males and females vary in many characteristics that typically underlie how well a host is able to fight infection, such as body-size, immune capacity, or energy availability. Although well studied in the context of sexual signalling, there is now growing recognition that these differences can influence aspects of pathogen evolution as well. Here we consider how co-infection between multiple pathogen strains is shaped by male-female differences. In natural populations, infections by more than one pathogen strain or species are believed to be a widespread occurrence. Using the water flea, Daphnia magna, we exposed genetically identical males and females to replicated bacterial co-infections. We found that pathogen transmission and virulence were much higher in females. However, males did not simply lower average pathogen fitness, but rather the influence of co-infection was more varied and less defined than in females. We discuss how pathogens may have more fitness benefits to gain, and consequently to lose, when infecting one sex over the other.

The evolution of sexual dimorphism and its potential impact on host-pathogen coevolution.

Sex and infection are intimately linked. Many diseases are spread by sexual contact, males are thought to evolve exaggerated sexual signals to demonstrate their immune robustness, and pathogens have been shown to direct the evolution of recombination. In all of these examples, infection is influencing the evolution of male and female fitness, but less is known about how sex differences influence pathogen fitness. A defining characteristic of sexual dimorphism is not only divergent phenotypes, but also a complex genetic architecture involving changes in genetic correlations among shared fitness traits, and differences in the accumulation of mutations-all of which may affect selection on an invading pathogen. Here, we outline the implications that the genetics of sexual dimorphism can have for host-pathogen coevolution and argue that male-female differences influence more than just the environment that a pathogen experiences.