Th17-related cytokines contribute to recall-like expansion/effector function of HMBPP-specific Vγ2Vδ2 T cells after Mycobacterium tuberculosis infection or vaccination: Immunity to infection

Whether cytokines can influence the adaptive immune response by antigen-specific γδ T cells during infections or vaccinations remains unknown. We previously demonstrated that, during BCG/Mycobacterium tuberculosis (Mtb) infections, Th17-related cytokines markedly upregulated when phosphoantigen-specific VγVδ2 T cells expanded. In this study, we examined the involvement of Th17-related cytokines in the recall-like responses of Vγ2Vδ2 T cells following Mtb infection or vaccination against TB. Treatment with IL-17A/IL-17F or IL-22 expanded phosphoantigen 4-hydroxy-3-methyl-but-enyl pyrophosphate (HMBPP)-stimulated Vγ2Vδ2 T cells from BCG-vaccinated macaques but not from naïve animals, and IL-23 induced greater expansion than the other Th17-related cytokines. Consistently, Mtb infection of macaques also enhanced the ability of IL-17/IL-22 or IL-23 to expand HMBPP-stimulated Vγ2Vδ2 T cells. When evaluating IL-23 signaling as a prototype, we found that HMBPP/IL-23-expanded Vγ2Vδ2 T cells from macaques infected with Mtb or vaccinated with BCG or Listeria ΔactA prfA*-ESAT6/Ag85B produced IL-17, IL-22, IL-2, and IFN-γ. Interestingly, HMBPP/IL-23-induced production of IFN-γ in turn facilitated IL-23-induced expansion of HMBPP-activated Vγ2Vδ2 T cells. Furthermore, HMBPP/IL-23-induced proliferation of Vγ2Vδ2 T cells appeared to require APC contact and involve the conventional and novel protein kinase C signaling pathways. These findings suggest that Th17-related cytokines can contribute to recall-like expansion and effector function of Ag-specific γδ T cells after infection or vaccination

Reinforcement selection acting on the European house mouse hybrid zone

Behavioural isolation may lead to complete speciation when partial postzygotic isolation acts in the presence of divergent‐specific mate‐recognition systems. These conditions exist where Mus musculus musculus and M. m. domesticus come into contact and hybridize. We studied two mate‐recognition signal systems, based on urinary and salivary proteins, across a Central European portion of the mouse hybrid zone. Introgression of the genomic regions responsible for these signals: the major urinary proteins (MUPs) and androgen binding proteins (ABPs), respectively, was compared to introgression at loci assumed to be nearly neutral and those under selection against hybridization. The preference of individuals taken from across the zone regarding these signals was measured in Y mazes, and we develop a model for the analysis of the transition of such traits under reinforcement selection. The strongest assortative preferences were found in males for urine and females for ABP. Clinal analyses confirm nearly neutral introgression of an Abp locus and two loci closely linked to the Abp gene cluster, whereas two markers flanking the Mup gene region reveal unexpected introgression. Geographic change in the preference traits matches our reinforcement selection model significantly better than standard cline models. Our study confirms that behavioural barriers are important components of reproductive isolation between the house mouse subspecies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86873/1/j.1365-294X.2011.05106.x.pd

Host T Cell Responses to Malaria, Acquired Immunodeficiency Virus, and Listeria Infections

Understanding of T cell responses during infections will be vital to rational vaccine design. Malaria and AIDS represent two leading causes of death from infectious diseases worldwide, and their high geographic overlap means coinfection is prevalent. It remains unknown whether distinct immune responses during malaria/HIV coinfection dictate clinical outcomes. We tested this hypothesis by employing macaque models of malaria/simian-human immunodeficiency virus (SHIV) coinfection. P. fragile malaria coinfection of acutely-SHIV-infected macaques induced hyper-immune-activation and remarkable expansion of CD4+ and CD8+ T effector cells producing IFNγ or TNFα de novo. Malaria-driven cellular hyper-activation/expansion and high-level Th1-cytokines enhanced SHIV disease characterized by enhancing CD4+ T-cell depletion, profound lymphoid depletion/destruction and even necrosis in lymph nodes and spleens. Importantly, malaria/SHIV-mediated lymphoid depletion, destruction and necrosis in lymphoid tissues led to bursting parasite replication and fatal virus-associated malaria. Surprisingly, chronically-SHIV-infected macaques without AIDS employed different defense mechanisms during malaria coinfection, and mounted unique ~200-fold expansion of IL-17+/IL-22+ T-effectors with profound Th1 suppression. Such remarkable expansion of Th17/Th22 cells and inhibition of Th1 response coincided with development of immunity against fatal virus-associated malaria without accelerating SHIV disease. These novel findings suggest that virus infection status and selected Th1 or Th17/Th22 responses after malaria/AIDS virus coinfection contribute to distinct outcomes of virus infection and malaria. In addition, Vγ2Vδ2 T cells were not expanded during malaria infection of macaques, despite being expanded in human malaria infection. Vγ2Vδ2 T cells were expanded during L. monocytogenes infection, and exhibited various effector functions, including production of cytokines and the ability to directly lyse infected cells. By determining how T cells are activated during infection and what protective immune functions are, we can aid rational vaccine design against a variety of pathogens

Bacillus subtilis Biofilms: a Matter of Individual Choice

Bacillus subtilis has the capacity to choose between two mutually exclusive lifestyles: biofilm formation and flagellum-mediated swimming motility. Interestingly, this choice is made at the individual cell level, with bacterial cells in a population expressing genes required for biofilm formation or genes required for swimming motility but not both.Bacillus subtilis has the capacity to choose between two mutually exclusive lifestyles: biofilm formation and flagellum-mediated swimming motility. Interestingly, this choice is made at the individual cell level, with bacterial cells in a population expressing genes required for biofilm formation or genes required for swimming motility but not both. A bistable switch controls the biofilm-versus-swimming decision, resulting in an evolutionarily favorable strategy known as “bet hedging” that ensures that subpopulations of bacteria continue to grow as conditions change and/or become unfavorable. In a recent issue of mBio, J. Kampf and colleagues (mBio 9:e01464-18, 2018, https://doi.org/10.1128/mBio.01464-18) reported the use of a combination of genetics and microfluidics to reveal that the interplay that occurs between the SinR and YmdB proteins underlies the B. subtilis choice between biofilm formation and swimming motility. Their report suggests that B. subtilis experiences selective pressure to form biofilms while maintaining reserve cell subpopulations with the capacity to swim away

MMGray_GoughIslandMouseDemographicHistory_Microsatellite_GenAlEx_Format

Raw microsatellite genotypes in GenAlEx format

SeqSampleInformation

Sample information, accessions, and raw sequence

MainModel

ABC toolbox model files (ms was the coalescent simulatior, MarkSim was used to generate mutations, arlsumstat was the summary statistic calculator) See ABC toolbox manual for more details

Data from: Demographic history of a recent invasion of house mice on the isolated Island of Gough

Island populations provide natural laboratories for studying key contributors to evolutionary change, including natural selection, population size, and the colonization of new environments. The demographic histories of island populations can be reconstructed from patterns of genetic diversity. House mice (Mus musculus) inhabit islands throughout the globe, making them an attractive system for studying island colonization from a genetic perspective. Gough Island, in the central South Atlantic Ocean, is one of the remotest islands in the world. House mice were introduced to Gough Island by sealers during the 19th century, and display unusual phenotypes, including exceptionally large body size and carnivorous feeding behavior. We describe genetic variation in Gough Island mice using mitochondrial sequences, nuclear sequences, and microsatellites. Phylogenetic analysis of mitochondrial sequences suggested that Gough Island mice belong to Mus musculus domesticus, with the maternal lineage possibly originating in England or France. Cluster analyses of microsatellites revealed genetic membership for Gough Island mice in multiple coastal populations in Western Europe, suggesting admixed ancestry. Gough Island mice showed substantial reductions in mitochondrial and nuclear sequence variation and weak reductions in microsatellite diversity compared with Western European populations, consistent with a population bottleneck. Approximate Bayesian Computation (ABC) estimated that mice recently colonized Gough Island (~100 years ago) and experienced a 98% reduction in population size followed by a rapid expansion. Our results indicate that the unusual phenotypes of Gough Island mice evolved rapidly, positioning these mice as useful models for understanding rapid phenotypic evolution