Immunogenetics

Buckley, Katherine M.; Yoder, Jeffrey A.

doi: 10.1007/s00251-021-01243-4pmid: 34910229

Maruta, Natsumi; Burdett, Hayden; Lim, Bryan Y. J.; Hu, Xiahao; Desa, Sneha; Manik, Mohammad Kawsar; Kobe, Bostjan

doi: 10.1007/s00251-021-01242-5pmid: 34981187

Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.

Nicotra, Matthew L.

doi: 10.1007/s00251-021-01233-6pmid: 34773127

Hydractinia symbiolongicarpus is a colonial hydroid and a long-standing model system for the study of invertebrate allorecognition. The Hydractinia allorecognition system allows colonies to discriminate between their own tissues and those of unrelated conspecifics that co-occur with them on the same substrate. This recognition mediates spatial competition and mitigates the risk of stem cell parasitism. Here, I review how we have come to our current understanding of the molecular basis of allorecognition in Hydractinia. To date, two allodeterminants have been identified, called Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2), which occupy a genomic region called the allorecognition complex (ARC). Both genes encode highly polymorphic cell surface proteins that are capable of homophilic binding, which is thought to be the mechanism of self/non-self discrimination. Here, I review how we have come to our current understanding of Alr1 and Alr2. Although both are members of the immunoglobulin superfamily, their evolutionary origins remain unknown. Moreover, existing data suggest that the ARC may be home to a family of Alr-like genes, and I speculate on their potential functions.

Liegeois, Samuel; Ferrandon, Dominique

doi: 10.1007/s00251-021-01239-0pmid: 35092465

Insects occupy a central position in the biosphere. They are able to resist infections even though they lack an adaptive immune system. Drosophila melanogaster has been used as a potent genetic model to understand innate immunity both in invertebrates and vertebrates. Its immune system includes both humoral and cellular arms. Here, we review how the distinct immune responses are triggered upon sensing infections, with an emphasis on the mechanisms that lead to systemic humoral immune responses. As in plants, the components of the cell wall of microorganisms are detected by dedicated receptors. There is also an induction of the systemic immune response upon sensing the proteolytic activities of microbial virulence factors. The antiviral response mostly relies on sensing double-stranded RNAs generated during the viral infection cycle. This event subsequently triggers either the viral short interfering RNA pathway or a cGAS-like/STING/NF-κB signaling pathway.

Pujol, Nathalie; Ewbank, Jonathan J.

doi: 10.1007/s00251-021-01231-8pmid: 34761293

The natural environment of the free-living nematode Caenorhabditis elegans is rich in pathogenic microbes. There is now ample evidence to indicate that these pathogens exert a strong selection pressure on C. elegans, and have shaped its genome, physiology, and behaviour. In this short review, we concentrate on how C. elegans stands out from other animals in terms of its immune repertoire and innate immune signalling pathways. We discuss how C. elegans often detects pathogens because of their effects on essential cellular processes, or organelle integrity, in addition to direct microbial recognition. We illustrate the extensive molecular plasticity that is characteristic of immune defences in C. elegans and highlight some remarkable instances of lineage-specific innovation in innate immune mechanisms.

Pujol, Nathalie; Ewbank, Jonathan J.

doi: 10.1007/s00251-021-01241-6pmid: 34882258

Li, Hongyu; Gharamah, Abdullah A.; Hambrook, Jacob R.; Wu, Xinzhong; Hanington, Patrick C.

doi: 10.1007/s00251-021-01236-3pmid: 34854945

The immune cells of the snail Biomphalaria glabrata are classified into hyalinocyte and granulocyte subtypes. Both subtypes are essential for the proper functioning of the snail immune response, which we understand best within the context of how it responds to challenge with the human parasite Schistosoma mansoni. Granulocytes are adherent phagocytic cells that possess conspicuous granules within the cell cytoplasm. Hyalinocytes, on the other hand, are predominantly non-adherent and are known to produce a handful of anti-S. mansoni immune effectors. While our understanding of these cells has progressed, an in-depth comparison of the functional capabilities of each type of immune cell has yet to be undertaken. Here, we present the results of a single-cell RNA-seq study in which single granulocytes and hyalinocytes from S. mansoni-susceptible M-line B. glabrata and S. mansoni-resistant BS-90 B. glabrata are compared without immune stimulation. This transcriptomic analysis supports a role for the hyalinocytes as producers of immune effectors such as biomphalysin and thioester-containing proteins. It suggests that granulocytes are primarily responsible for producing fibrinogen-related proteins and are armed with various pattern-recognition receptors such as toll-like receptors with a confirmed role in the anti-S. mansoni immune response. This analysis also confirms that the granulocytes and hyalinocytes of BS-90 snails are generally more immunologically prepared than their M-line counterparts. As the first single-cell analysis of the transcriptional profiles of B. glabrata immune cells, this study provides crucial context for understanding the B. glabrata immune response. It sets the stage for future investigations into how each immune cell subtype differs in its response to various immunological threats.

Liberti, Assunta; Natarajan, Ojas; Atkinson, Celine Grace F.; Dishaw, Larry J.

doi: 10.1007/s00251-021-01237-2pmid: 34988622

The origins of a “pass-through” gut in early bilaterians facilitated the exploration of new habitats, motivated the innovation of feeding styles and behaviors, and helped drive the evolution of more complex organisms. The gastrointestinal tract has evolved to consist of a series of interwoven exchanges between nutrients, host immunity, and an often microbe-rich environmental interface. Not surprisingly, animals have expanded their immune repertoires to include soluble effectors that can be secreted into luminal spaces, e.g., in the gut, facilitating interactions with microbes in ways that influence their settlement dynamics, virulence, and their interaction with other microbes. The immunoglobulin (Ig) domain, which is also found in some non-immune molecules, is recognized as one of the most versatile recognition domains lying at the interface of innate and adaptive immunity; among vertebrates, secreted Igs are known to play crucial roles in the management of gut microbial communities. In this mini-review, we will focus on secreted immune effectors possessing Ig-like domains in invertebrates, such as the fibrinogen-related effector proteins first described in the gastropod Biomphalaria glabrata, the Down syndrome cellular adhesion molecule first described in the arthropod, Drosophila melanogaster, and the variable region-containing chitin-binding proteins of the protochordates. We will highlight our current understanding of their function and their potential role, if not yet recognized, in the establishment and maintenance of host-microbial interfaces and argue that these Igs are likely also essential to microbiome management.

Dornburg, Alex; Yoder, Jeffrey A.

doi: 10.1007/s00251-021-01232-7pmid: 34981186

For over half a century, deciphering the origins of the genomic loci that form the jawed vertebrate adaptive immune response has been a major topic in comparative immunogenetics. Vertebrate adaptive immunity relies on an extensive and highly diverse repertoire of tandem arrays of variable (V), diversity (D), and joining (J) gene segments that recombine to produce different immunoglobulin (Ig) and T cell receptor (TCR) genes. The current consensus is that a recombination-activating gene (RAG)-like transposon invaded an exon of an ancient innate immune VJ-bearing receptor, giving rise to the extant diversity of Ig and TCR loci across jawed vertebrates. However, a model for the evolutionary relationships between extant non-recombining innate immune receptors and the V(D)J receptors of the jawed vertebrate adaptive immune system has only recently begun to come into focus. In this review, we provide an overview of non-recombining VJ genes, including CD8β, CD79b, natural cytotoxicity receptor 3 (NCR3/NKp30), putative remnants of an antigen receptor precursor (PRARPs), and the multigene family of signal-regulatory proteins (SIRPs), that play a wide range of roles in immune function. We then focus in detail on the VJ-containing novel immune-type receptors (NITRs) from ray-finned fishes, as recent work has indicated that these genes are at least 50 million years older than originally thought. We conclude by providing a conceptual model of the evolutionary origins and phylogenetic distribution of known VJ-containing innate immune receptors, highlighting opportunities for future comparative research that are empowered by this emerging evolutionary perspective.

Suurväli, Jaanus; Garroway, Colin J.; Boudinot, Pierre

doi: 10.1007/s00251-021-01235-4pmid: 34850255

B30.2 domains, also known as PRY/SPRY, are key components of specific subsets of two large families of proteins involved in innate immunity: the tripartite motif proteins (TRIMs) and the Nod-like receptors (NLRs). TRIM proteins are important, often inducible factors of antiviral innate immunity, targeting multiple steps of viral cycles through a variety of mechanisms. NLRs prime and regulate systemic innate defenses, especially against bacteria, and control inflammation. Large TRIM and NLR subsets characterized by the presence of a B30.2 domain have been reported from a few fish species including zebrafish and seem to be strongly prone to gene duplication/expansion. Here, we performed a large-scale survey of these receptors across about 150 fish genomes, focusing on ray-finned fishes. We assessed the number and genomic distribution of domains and domain combinations associated with TRIMs, NLRs, and other genes containing B30.2 domains and looked for gene expansion patterns across fish groups. We then used a model to test the impact of taxonomy, genome size, and environmental variables on the copy numbers of these genes. Our findings reveal novel domain structures, clade-specific gains and losses. They also assist with the timing of the gene expansions, reveal patterns associated with the MHC, and lay the groundwork for further studies delving deeper into the forces that drive the copy number variation of immune genes on a species level.