Influence of surgery and dexamethasone on cell-mediated immune responses in patients with meningiomas.

Cell-mediated cytotoxicity (CTX) was studied in meningioma patients before and within 2 weeks of complete excision of the tumour, using the [3H]-prolin- microcytotoxicity test. Three of 7 patients tested before surgery showed specific CTX, 2 revealed a "non-specific" (tumour-unrelated) response, and 2 were non-reactive. After surgery, CTX decreased from 84 to 50% in one patient and became negative in 2 others previously positive. One of 2 patients showing "non-specific" CTX preoperatively became positive, while the other remained unchanged. All patients were receiving dexamethasone (DXM) at the time they were tested. Lymphocyte responses to PHA were not significantly different before or after surgery (i.e. after prolonged treatment with DXM), from healthy controls. Blocking activity could be detected in the sera of all 3 patients before surgery. This activity was not specific for meningiomas. Paradoxically, the same sera did not inhibit the proliferative response to PHA. Serum from only one patient consistently suppressed the blastogenic response of homologous lymphocytes to PHA. Inhibitory activity was associated with the IgG fraction of his serum

The functional repertoire contained within the native microbiota of the model nematode Caenorhabditis elegans

The microbiota is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiota of the model nematode Caenorhabditis elegans. We integrated whole-genome sequences of 77 bacterial microbiota members with metabolic modeling and experimental characterization of bacterial physiology. We found that, as a community, the microbiota can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses revealed that nutrient context can influence how bacteria interact within the microbiota. We identified key bacterial traits that are likely to influence the microbe’s ability to colonize C. elegans (i.e., the ability of bacteria for pyruvate fermentation to acetoin) and affect nematode fitness (i.e., bacterial competence for hydroxyproline degradation). Considering that the microbiota is usually neglected in C. elegans research, the resource presented here will help our understanding of this nematode’s biology in a more natural context. Our integrative approach moreover provides a novel, general framework to characterize microbiota-mediated functions

High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates.

A key question in current immunity research is how the innate immune system can generate high levels of specificity. Evidence is accumulating that invertebrates, which exclusively rely on innate defense mechanisms, can differentiate between pathogens on the species and even strain level. In this review, we identify and discuss the particular potential of C-type lectin-like domain (CTLD) proteins to generate high immune specificity. Whilst several CTLD proteins are known to act as pattern recognition receptors in the vertebrate innate immune system, the exact role of CTLD proteins in invertebrate immunity is much less understood. We show that CTLD genes are highly abundant in most metazoan genomes and summarize the current state of knowledge on CTLD protein function in insect, crustacean and nematode immune systems. We then demonstrate extreme CTLD gene diversification in the genomes of Caenorhabditis nematodes and provide an update of data from CTLD gene function studies in C. elegans, which indicate that the diversity of CTLD genes could contribute to immune specificity. In spite of recent achievements, the exact functions of the diversified invertebrate CTLD genes are still largely unknown. Our review therefore specifically discusses promising research approaches to rectify this knowledge gap

The genomic basis of Red Queen dynamics during rapid reciprocal host–pathogen coevolution

Pathogens are omnipresent and by definition detrimental to their hosts. Pathogens thus exert high selection on their hosts, which, if adapting, can exert similar levels of selection on the pathogen, resulting in ongoing cycles of reciprocal adaptation between the antagonists. Such coevolutionary interactions have a central influence on the evolution of organisms. Surprisingly, we still know little about the exact selection dynamics and the genome regions involved. Our study uses a controlled experimental approach with an animal host to dissect coevolutionary selection. We find that distinct selective processes underlie rapid coadaptation in the two antagonists, including antagonistic frequency-dependent selection on toxin gene copy number in the pathogen, while the host response is likely influenced by changes in multiple genome regions.Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria–}phage systems or only one of the antagonists of a eukaryotic host{–}pathogen interaction. We add to our understanding of these important coevolutionary interactions using an experimental host{–pathogen model, which includes the nematode Caenorhabditis elegans and its pathogen Bacillus thuringiensis. We combined experimental evolution with time-shift experiments, in which a focal host or pathogen is tested against a coevolved antagonist from the past, present, or future, followed by genomic analysis. We show that (i) coevolution occurs rapidly within few generations, (ii) temporal coadaptation at the phenotypic level is found in parallel across replicate populations, consistent with antagonistic frequency-dependent selection, (iii) genomic changes in the pathogen match the phenotypic pattern and include copy number variations of a toxin-encoding plasmid, and (iv) host genomic changes do not match the phenotypic pattern and likely involve selective responses at more than one locus. By exploring the dynamics of coevolution at the phenotypic and genomic level for both host and pathogen simultaneously, our findings demonstrate a more complex model of the Red Queen, consisting of distinct selective processes acting on the two antagonists during rapid and reciprocal coadaptation

The genomic basis of Red Queen dynamics during rapid reciprocal host-pathogen coevolution

Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria-phage systems or only one of the antagonists of a eukaryotic host-pathogen interaction. We add to our understanding of these important coevolutionary interactions using an experimental host-pathogen model, which includes the nematode Caenorhabditis elegans and its pathogen Bacillus thuringiensis We combined experimental evolution with time-shift experiments, in which a focal host or pathogen is tested against a coevolved antagonist from the past, present, or future, followed by genomic analysis. We show that (i) coevolution occurs rapidly within few generations, (ii) temporal coadaptation at the phenotypic level is found in parallel across replicate populations, consistent with antagonistic frequency-dependent selection, (iii) genomic changes in the pathogen match the phenotypic pattern and include copy number variations of a toxin-encoding plasmid, and (iv) host genomic changes do not match the phenotypic pattern and likely involve selective responses at more than one locus. By exploring the dynamics of coevolution at the phenotypic and genomic level for both host and pathogen simultaneously, our findings demonstrate a more complex model of the Red Queen, consisting of distinct selective processes acting on the two antagonists during rapid and reciprocal coadaptation

Supplementary Material for: High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates

A key question in current immunity research is how the innate immune system can generate high levels of specificity. Evidence is accumulating that invertebrates, which exclusively rely on innate defense mechanisms, can differentiate between pathogens on the species and even strain level. In this review, we identify and discuss the particular potential of C-type lectin-like domain (CTLD) proteins to generate high immune specificity. Whilst several CTLD proteins are known to act as pattern recognition receptors in the vertebrate innate immune system, the exact role of CTLD proteins in invertebrate immunity is much less understood. We show that CTLD genes are highly abundant in most metazoan genomes and summarize the current state of knowledge on CTLD protein function in insect, crustacean and nematode immune systems. We then demonstrate extreme CTLD gene diversification in the genomes of <i>Caenorhabditis </i>nematodes and provide an update of data from CTLD gene function studies in <i>C. elegans</i>, which indicate that the diversity of CTLD genes could contribute to immune specificity. In spite of recent achievements, the exact functions of the diversified invertebrate CTLD genes are still largely unknown. Our review therefore specifically discusses promising research approaches to rectify this knowledge gap

Effector and regulator: Diverse functions of C. elegans C-type lectin-like domain proteins

In C. elegans, 283 clec genes encode a highly diverse family of C-type lectin-like domain (CTLD) proteins. Since vertebrate CTLD proteins have characterized functions in defense responses against pathogens and since expression of C. elegans clec genes is pathogen-dependent, it is generally assumed that clec genes function in C. elegans immune defenses. However, little is known about the relative contribution and exact function of CLEC proteins in C. elegans immunity. Here, we focused on the C. elegans clec gene clec-4, whose expression is highly upregulated by pathogen infection, and its paralogs clec-41 and clec-42. We found that, while mutation of clec-4 resulted in enhanced resistance to the Gram-positive pathogen Bacillus thuringiensis MYBt18247 (Bt247), inactivation of clec-41 and clec-42 by RNAi enhanced susceptibility to Bt247. Further analyses revealed that enhanced resistance of clec-4 mutants to Bt247 was due to an increase in feeding cessation on the pathogen and consequently a decrease in pathogen load. Moreover, clec-4 mutants exhibited feeding deficits also on non-pathogenic bacteria that were in part reflected in the clec-4 gene expression profile, which overlapped with gene sets affected by starvation or mutation in nutrient sensing pathways. However, loss of CLEC-4 function only mildly affected life-history traits such as fertility, indicating that clec-4 mutants are not subjected to dietary restriction. While CLEC-4 function appears to be associated with the regulation of feeding behavior, we show that CLEC-41 and CLEC-42 proteins likely function as bona fide immune effector proteins that have bacterial binding and antimicrobial capacities. Together, our results exemplify functional diversification within clec gene paralogs. © 2021 Pees et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited