AUTHOR=Svenning Steingrim , Gondek-Wyrozemska Agata T. , van der Wal Yorick Andreas , Robertsen Børre , Jensen Ingvill , Jørgensen Jorunn B. , Edholm Eva-Stina 

TITLE=Microbial Danger Signals Control Transcriptional Induction of Distinct MHC Class I L Lineage Genes in Atlantic Salmon

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02425

DOI=10.3389/fimmu.2019.02425

ISSN=1664-3224

ABSTRACT=<p>Antigen processing and presentation by major histocompatibility complex (MHC) molecules is a cornerstone in vertebrate immunity. Like mammals, teleosts possess both classical MHC class I and multiple families of divergent MHC class I genes. However, while certain mammalian MHC class I-like molecules have proven to be integral in immune regulation against a broad array of pathogens, the biological relevance of the different MHC class I lineages in fish remains elusive. This work focuses on MHC class I L lineage genes and reveals unique regulatory patterns of six genes (<italic>Sasa</italic>-<italic>lia, Sasa</italic>-<italic>lda, Sasa</italic>-<italic>lca, Sasa</italic>-<italic>lga, Sasa</italic>-<italic>lha</italic>, and <italic>Sasa</italic>-<italic>lfa</italic>) in antimicrobial immunity of Atlantic salmon (<italic>Salmo salar L</italic>.). Using two separate <italic>in vivo</italic> challenge models with different kinetics and immune pathologies combined with <italic>in vitro</italic> stimulation using viral and bacterial TLR ligands, we show that <italic>de novo</italic> synthesis of different L lineage genes is distinctly regulated in response to various microbial stimuli. Prior to the onset of classical MHC class I gene expression, <italic>lia</italic> was rapidly and systemically induced <italic>in vivo</italic> by the single-stranded (ss) RNA virus salmonid alpha virus 3 (SAV3) but not in response to the intracellular bacterium <italic>Piscirickettsia salmonis</italic>. In contrast, <italic>lga</italic> expression was upregulated in response to both viral and bacterial stimuli. A role for distinct MHC class I L-lineage genes in anti-microbial immunity in salmon was further substantiated by a marked upregulation of <italic>lia</italic> and <italic>lga</italic> gene expression in response to type I IFNa stimulation <italic>in vitro</italic>. Comparably, <italic>lha</italic> showed no transcriptional induction in response to IFNa stimulation but was strongly induced in response to a variety of viral and bacterial TLR ligands. In sharp contrast, <italic>lda</italic> showed no response to viral or bacterial challenge. Similarly, induction of <italic>lca</italic>, which is predominantly expressed in primary and secondary lymphoid tissues, was marginal with the exception of a strong and transient upregulation in pancreas following SAV3 challenge Together, these findings suggest that certain Atlantic salmon MHC class I L lineage genes play important and divergent roles in early anti-microbial response and that their regulation, in response to different activation signals, represents a system for selectively promoting the expression of distinct non-classical MHC class I genes in response to different types of immune challenges.</p>