scholarly journals Borrelia burgdorferi sensu lato infection pressure shapes innate immune gene evolution in natural rodent populations across Europe

2015 ◽  
Vol 11 (5) ◽  
pp. 20150263 ◽  
Author(s):  
Barbara Tschirren

Although parasite-mediated selection is assumed to be the main driver of immune gene evolution, empirical evidence that parasites induce allele frequency changes at host immune genes in time and/or space remains scarce. Here, I show that the frequency of a protective gene variant of the innate immune receptor Toll-like receptor 2 in natural bank vole ( Myodes glareolus ) populations is positively associated with the strength of Borrelia burgdorferi sensu lato infection risk across the European continent. Thereby, this study provides rare evidence for the role of spatially variable infection pressures in moulding the vertebrate immune system.

2013 ◽  
Vol 56 (1) ◽  
pp. 691-699
Author(s):  
T. Zhang ◽  
N. Zhao ◽  
Q. Liu

Abstract. To research effects of the artificial selection of Gallus gallus on G. domesticus' nucleotide diversity of immune genes, sequence polymorphisms of G. domesticus (23 genes), G. gallus (23 genes), G. lafayetti (17 genes), and G. sonneratii (17 genes) were obtained from GenBank. The data set included 819 polymorphisms. Immune gene polymorphism and selection efficiency in the data from those four species of Gallus were calculated. By calculating the qw (Watterson's estimator) of each site, an average qw for each species and the minimum number of re-combinations in each species and by estimating the selection efficiency for G. domesticus and G. gallus, neither significant nucleotide diversity nor genetic-diversity-qw- difference was found between G. domesticus and G. gallus. The results indicated that the patterns of genetic diversity in G. domesticus were strongly influenced by recombination and, because Tajima's D has a negative value, recombination was the main mechanism responsible for the immune gene evolution of G. gallus.


2018 ◽  
Author(s):  
David Reher ◽  
Felix M. Key ◽  
Aida M. Andrés ◽  
Janet Kelso

Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, and particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups and at different time points on the Neandertal lineage with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).We find that the two Neandertals and the Denisovan have similar gene diversity, both significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared to the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.


2011 ◽  
Vol 77 (16) ◽  
pp. 5716-5721 ◽  
Author(s):  
M. Marsot ◽  
M. Sigaud ◽  
J. L. Chapuis ◽  
E. Ferquel ◽  
M. Cornet ◽  
...  

ABSTRACTLittle attention has been given in scientific literature to how introduced species may act as a new host for native infectious agents and modify the epidemiology of a disease. In this study, we investigated whether an introduced species, the Siberian chipmunk (Tamias sibiricus barberi), was a potentially new reservoir host forBorrelia burgdorferisensu lato, the causative agent of Lyme disease. First, we ascertained whether chipmunks were infected by all of theB. burgdorferisensu lato genospecies associated with rodents and available in their source of infection, questing nymphs. Second, we determined whether the prevalence and diversity ofB. burgdorferisensu lato in chipmunks were similar to those of a native reservoir rodent, the bank vole (Myodes glareolus). Our research took place between 2006 and 2008 in a suburban French forest, where we trapped 335 chipmunks and 671 voles and collected 743 nymphs of ticks that were questing for hosts by dragging on the vegetation. We assayed forB. burgdorferisensu lato with ear biopsy specimens taken from the rodents and in nymphs using PCR and restriction fragment length polymorphism (RFLP). Chipmunks were infected by the threeBorreliagenospecies that were present in questing nymphs and that infect rodents (B. burgdorferisensu stricto,B. afzelii, andB. garinii). In contrast, voles hosted onlyB. afzelii. Furthermore, chipmunks were more infected (35%) than voles (16%). These results may be explained by the higher exposure of chipmunks, because they harbor more ticks, or by their higher tolerance of otherB. burgdorferisensu lato genospecies than ofB. afzelii. If chipmunks are competent reservoir hosts forB. burgdorferisensu lato, they may spill backB. burgdorferisensu lato to native communities and eventually may increase the risk of Lyme disease transmission to humans.


2012 ◽  
Vol 80 (10) ◽  
pp. 3343-3359 ◽  
Author(s):  
Abul K. Azad ◽  
Wolfgang Sadee ◽  
Larry S. Schlesinger

ABSTRACTTuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.


2013 ◽  
Vol 58 (3) ◽  
Author(s):  
Jakub Netušil ◽  
Alena Žákovská ◽  
Karel Vostal ◽  
Adam Norek ◽  
Michal Stanko

AbstractTicks represent the primary vectors of several serious diseases, including the Lyme disease caused by Borrelia burgdorferi sensu lato (Bbsl). In this study two dominant ectoparasitic groups of arthropods (Mesostigmata, Siphonaptera) were investigated for the presence of borrelian DNA in order to determine their potential role of vectors (or carriers) of this bacterium. All individuals (235) were collected from wild-living rodents obtained in three localities in the Czech Republic (Bažantula, Baba and Křižovice). The majority of parasites were members of the families Parasitidae and Dermanyssidae (Mesostigmata) and families Hystrichopsyllidae and Ceratophyllidae (Siphonaptera). The rodent host species was almost exclusively the yellow-necked mouse (Apodemus flavicollis). Bbsl was detected by the PCR method in the following ectoparasite species: Euryparasitus emarginatus (1), Eulaelaps stabularis (1), Haemogamassus nidi (1), Laelaps agilis (5), Myonyssus gigas (1) (Mesostigmata) and Ctenophthalmus agyrtes (1), C. solutus (3) (Siphonaptera).


2019 ◽  
Author(s):  
Wen-Hao Tan ◽  
Andrew J. Mongue ◽  
Jacobus C. de Roode ◽  
Nicole M. Gerardo ◽  
James R. Walters

ABSTRACTImmune genes presumably rapidly evolve as pathogens exert strong selection pressures on host defense, but the evolution of immune genes is also constrained by trade-offs with other biological functions and shaped by the environmental context. Thus, immune genes may exhibit complex evolutionary patterns, particularly when organisms disperse to or live in variable environments. We examined the evolutionary patterns of the full set of known canonical immune genes within and among populations of monarch butterflies (Danaus plexippus), and relative to a closely related species (D. gilippus). Monarchs represent a system with a known evolutionary history, in which North American monarchs dispersed to form novel populations across the world, providing an opportunity to explore the evolution of immunity in the light of population expansion into novel environments. By analyzing a whole-genome resequencing dataset across populations, we found that immune genes as a whole do not exhibit consistent patterns of selection, differentiation, or genetic variation, but that patterns are specific to functional classes. Species comparisons between D. plexippus and D. gilippus and analyses of monarch populations both revealed consistently low levels of genetic variation in signaling genes, suggesting conservation of these genes over evolutionary time. Modulation genes showed the opposite pattern, with signatures of relaxed selection across populations. In contrast, recognition and effector genes exhibited less consistent patterns. When focusing on genes with exceptionally strong signatures of selection or differentiation, we also found population-specific patterns, consistent with the hypothesis that monarch populations do not face uniform selection pressures with respect to immune function.


mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Claire D. James ◽  
Christian T. Fontan ◽  
Raymonde Otoa ◽  
Dipon Das ◽  
Apurva T. Prabhakar ◽  
...  

ABSTRACT Human papillomaviruses (HPV) are causative agents in 5% of all cancers, including the majority of anogenital and oropharyngeal cancers. Downregulation of innate immune genes (IIGs) by HPV to promote the viral life cycle is well documented; E6 and E7 are known repressors of these genes. More recently, we demonstrated that E2 could also repress IIGs. These studies have been carried out in cells overexpressing the viral proteins, and to further investigate the role of individual viral proteins in this repression, we introduced stop codons into E6 and/or E7 in the entire HPV16 genome and generated N/Tert-1 cells stably maintaining the HPV16 genomes. We demonstrate that E6 or E7 individually is not sufficient to repress IIG expression in the context of the entire HPV16 genome; both are required for a synergistic repression. The DNA damage response (DDR) is activated by HPV16 irrespective of E6 and E7 expression, presumably due to viral replication; E1 is a known activator of the DDR. In addition, replication stress was apparent in HPV16-positive cells lacking E6 and E7, manifested by attenuated cellular growth and activation of replication stress genes. These studies led us to the following model. Viral replication per se can activate the DDR following infection, and this activation is a known inducer of IIG expression, which may induce cellular senescence. To combat this, E6 and E7 synergistically combine to manipulate the DDR and actively repress innate immune gene expression promoting cellular growth; neither protein by itself is able to do this. IMPORTANCE The role of human papillomavirus 16 (HPV16) in human cancers is well established; however, to date there are no antiviral therapeutics that are available for combatting these cancers. To identify such targets, we must enhance the understanding of the viral life cycle. Innate immune genes (IIGs) are repressed by HPV16, and we have reported that this repression persists through to cancer. Reversal of this repression would boost the immune response to HPV16-positive tumors, an area that is becoming more important given the advances in immunotherapy. This report demonstrates that E6 and E7 synergistically repress IIG expression in the context of the entire HPV16 genome. Removal of either protein activates the expression of IIGs by HPV16. Therefore, gaining a precise understanding of how the viral oncogenes repress IIG expression represents an opportunity to reverse this repression and boost the immune response to HPV16 infections for therapeutic gain.


2020 ◽  
Author(s):  
KO West ◽  
AR Wagner ◽  
HM Scott ◽  
KJ Vail ◽  
K Carter ◽  
...  

ABSTRACTWhile the signaling cascades and transcription factors that activate gene expression in macrophages following pattern recognition receptor engagement are well known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Recent phosphoproteomics analyses revealed that members of the SR and hnRNP families of splicing regulatory proteins undergo dynamic post-translational modification in infected macrophages. To begin to test if these splicing factors play a privileged role in controlling the innate immune transcriptome, we analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage cell lines following infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (Salmonella). We observed that thousands of genes were up or downregulated in SR/hnRNP knockdown cells and differentially expressed genes (DEGs) varied significantly depending on the SR/hnRNP examined. We discovered that a subset of critical innate immune genes (Nos2, Mx1, Il1a) rely heavily on SR/hnRNPs for proper induction and/or repression, while others (Tnf, Il1b) are generally unaffected by splicing factor knockdown. We also discovered that many key immune sensors and signaling molecules are subject to regulation by alternative splicing. While our data does not provide evidence for positive correlation between a transcripts’ reliance of SR/hnRNPs for proper expression and the gene’s induction level, length, or intron/exon architecture, we found that many rapidly induced primary response genes are repressed by SR/hnRNPs. Consistent with SR/hnRNP proteins contributing to innate immune outcomes, knockdown of hnRNP K and U significantly enhanced the ability of RAW 264.7 macrophages to control viral replication. Based on these collective findings, we conclude that many innate immune genes have evolved to rely on one or more splicing regulatory factors to ensure the proper timing and magnitude of their induction, supporting a model wherein pre-splicing is a critical regulatory node in the innate immune response.


Author(s):  
Benjamin Young ◽  
Xaymara M. Serrano ◽  
Stephanie Rosales ◽  
Margaret W. Miller ◽  
Dana Williams ◽  
...  

AbstractCoral disease outbreaks are expected to increase in prevalence, frequency and severity due to climate change and other anthropogenic stressors. This is especially worrying for the Caribbean branching Acropora palmata which has already seen an 80% decrease in its coral cover, with this primarily due to disease. Despite the importance of this species, there has yet to be a characterization of its transcriptomic response to disease exposure. In this study we provide the first transcriptomic analysis of 12 A. palmata genotypes, and their symbiont Symbiodiniaceae, exposed to disease in 2016 and 2017. Year was the primary driver of sample variance for A. palmata and the Symbiodiniaceae. Lower expression of ribosomal genes in the coral, and higher expression of transmembrane ion transport genes in the Symbiodiniaceae indicate that the increased virulence in 2017 may have been due to a dysbiosis between the coral and Symbiodiniaceae. We also identified a conserved suite of innate immune genes responding to the disease challenge that was activated in both years. This included genes from the Toll-like receptor and lectin pathways, and antimicrobial peptides. Co-expression analysis identified a module positively correlated to disease exposure rich in innate immune genes, with D-amino acid oxidase, a gene implicated in phagocytosis and microbiome homeostasis, as the hub gene. The role of D-amino acid oxidase in coral immunity has not been characterized but holds potential as an important enzyme for responding to disease. Our results indicate that A. palmata mounts a similar immune response to disease exposure as other coral species previously studied, but with unique features that may be critical to the survival of this keystone Caribbean species.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 419
Author(s):  
Alena Žákovská ◽  
Eva Bártová ◽  
Pavlína Pittermannová ◽  
Marie Budíková

Wild small mammals are the most common reservoirs of pathogenic microorganisms that can cause zoonotic diseases. The aim of the study was to detect antibodies related to Borrelia burgdorferi sensu lato, Coxiella burnetii, and Francisella tularensis in wild small mammals from the Czech Republic. In total, sera or heart rinses of 211 wild small mammals (168 Apodemus flavicollis, 28 Myodes glareolus, 9 A. sylvaticus, and 6 Sorex araneus) were examined by modified enzyme-linked immunosorbent assay. Antibodies related to B.burgdorferi s.l., C. burnetii, and F. tularensis were detected in 15%, 19%, and 20% of animals, respectively. The prevalence of B. burgdorferi and F. tularensis statistically differed in localities and F. tularensis also differed in sex. Antibodies against 2–3 pathogens were found in 17% of animals with a higher prevalence in M. glareolus. This study brings new data about the prevalence of the above-mentioned pathogens.


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