Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphs

Abstract

ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse.

The genomic impact of historical hybridization with massive mitochondrial DNA introgression

“…Variants of these viruses are known to change host-specificity and affect other species, such as RHDV2 that affects hares [ 105 , 106 ] or EBHSV that affects American rabbits ( Sylvilagus ) [ 107 ]. Interestingly, one of the genes found here introgressed at high frequencies; interleukin 12B (IL12B) has been implicated in the inflammatory process and immune response to RHDV and Myxoma virus in rabbits [ 108 ], and to have adaptively introgressed from Neanderthals to modern humans in Europe [ 4 ]. These inferences thus strongly suggest that the invasion of new territories with new pathogenic pressures may have been facilitated by the incorporation of adapted genetic variants through introgression.…”

Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection

“…There are a couple of potential explanations for differences observed between the infection models. First, there are significant differences in the host proinflammatory response to invading pathogens between mice and rabbits, and as an example, IL-8 is a factor critical for neutrophil recruitment in humans and rabbits but is absent in mice [ 41 , 42 ]. While it is evident that proinflammatory mediators play a critical role in formation of S .…”

The remnant of the European rabbit (Oryctolagus cuniculus) IgD gene

“…Consistent with the rapid evolutionary divergence of rodents within the Euarchontoglires, the rabbit remnant Cδ exons are most closely related to the corresponding Cδ exons of primates, and most evolutionarily distant from those of the mouse and rat. Similarly, several additional immunologic genes have been reported to exhibit closer evolutionary relatedness between human and rabbit than between either and mouse [ 60 , 61 ]. Indeed, the evolutionary distance of the rabbit remnant Cδ exons from mouse and rat Cδ exons consistently exceeded that from species such as the horse, dog, sheep and pig, which belong to the superorder Laurasiatheria, a sister group to Euarchontoglires.…”