Browsing by Subject "immunity"

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  • Cui, Fuqiang; Wu, Hongpo; Safronov, Omid; Zhang, Panpan; Kumar, Rajeev; Kollist, Hannes; Salojärvi, Jarkko Tapani; Panstruga, Ralph; Overmyer, Kirk Loren (2018)
    The atmospheric pollutant ozone (O-3) is a strong oxidant that causes extracellular reactive oxygen species (ROS) formation, has significant ecological relevance, and is used here as a non-invasive ROS inducer to study plant signalling. Previous genetic screens identified several mutants exhibiting enhanced O-3 sensitivity, but few with enhanced tolerance. We found that loss-of-function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to powdery mildew disease, exhibit enhanced dose-dependent tolerance to O-3 and extracellular ROS, but a normal response to intracellular ROS. This phenotype is increased in a mlo2 mlo6 mlo12 triple mutant, reminiscent of the genetic redundancy of MLO genes in powdery mildew resistance. Stomatal assays revealed that enhanced O-3 tolerance in mlo2 mutants is not caused by altered stomatal conductance. We explored modulation of the mlo2-associated O-3 tolerance, powdery mildew resistance, and early senescence phenotypes by genetic epistasis analysis, involving mutants with known effects on ROS sensitivity or antifungal defence. Mining of publicly accessible microarray data suggests that these MLO proteins regulate accumulation of abiotic stress response transcripts, and transcript accumulation of MLO2 itself is O-3 responsive. In summary, our data reveal MLO2 as a novel negative regulator in plant ROS responses, which links biotic and abiotic stress response pathways.
  • Eskelinen, Eeva-Liisa (2019)
    Autophagy is a conserved catabolic process that delivers cytoplasmic components and organelles to lysosomes for degradation and recycling. This pathway serves to degrade nonfunctional organelles and aggregate-prone proteins, as well as to produce substrates for energy production and biosynthesis. Autophagy is especially important for the maintenance of stem cells, and for the survival and homeostasis of post-mitotic cells like neurons. Functional autophagy promotes longevity in several model organisms. Autophagy regulates immunity and inflammation at several levels and has both anti- and pro-tumorigenic roles in cancer. This review provides a concise overview of autophagy and its importance in cellular and organismal homeostasis, with emphasis on aging, stem cells, neuronal cells, immunity, inflammation, and cancer.
  • Cui, Fuqiang; Wenwu, Wu; Wang, Kai; Zhang, Yuan; Zhubing, Hu; Brosche, Mikael; Liu, Shenkui; Overmyer, Kirk (2019)
    Prevailing evidence indicates that abscisic acid (ABA) negatively influences immunity to the fungal pathogen Botrytis cinerea in most but not all cases. ABA is required for cuticle biosynthesis, and cuticle permeability enhances immunity to Botrytis via unknown mechanisms. This complex web of responses obscures the role of ABA in Botrytis immunity. Here, we addressed the relationships between ABA sensitivity, cuticle permeability, and Botrytis immunity in the Arabidopsis thaliana ABA-hypersensitive mutants protein phosphatase2c quadruple mutant (pp2c-q) and enhanced response to aba1 (era1-2). Neither pp2c-q nor era1-2 exhibited phenotypes predicted by the known roles of ABA; conversely, era1-2 had a permeable cuticle and was Botrytis resistant. We employed RNA-seq analysis in cuticle-permeable mutants of differing ABA sensitivities and identified a core set of constitutively activated genes involved in Botrytis immunity and susceptibility to biotrophs, independent of ABA signaling. Furthermore, botrytis susceptible1 (bos1), a mutant with deregulated cell death and enhanced ABA sensitivity, suppressed the Botrytis immunity of cuticle permeable mutants, and this effect was linearly correlated with the extent of spread of wound-induced cell death in bos1. Overall, our data demonstrate that Botrytis immunity conferred by cuticle permeability can be genetically uncoupled from PP2C-regulated ABA sensitivity, but requires negative regulation of a parallel ABA-dependent cell-death pathway.
  • Kiyuka, Patience Kerubo; Meri, Seppo; Khattab, Ayman (2020)
    The malaria parasite has for long been thought to escape host complement attack as a survival strategy. However, it was only recently that complement evasion mechanisms of the parasite were described. Simultaneously, the role of complement in antibody-mediated naturally acquired and vaccine-induced protection against malaria has also been reported. Such findings should be considered in future vaccine design, given the current need to develop more efficacious vaccines against malaria. Parasite antigens derived from molecules mediating functions crucial for parasite survival, such as complement evasion, or parasite antigens against which antibody responses lead to an efficient complement attack could present new candidates for vaccines. In this review, we discuss recent findings on complement evasion by the malaria parasites and the emerging role of complement in antibody-mediated protection against malaria. We emphasize that immune responses to vaccines based on complement inhibitors should not only induce complement-activating antibodies but also neutralize the escape mechanisms of the parasite.
  • Österlund, Michaela (Helsingfors universitet, 2017)
    Detta arbete är en litteraturstudie vars syfte är att undersöka vetenskapliga artiklar för att ta reda på hur D-vitamin påverkar parodontala vävnaden och om det finns belägg för att D-vitamin har en positiv effekt på parodontala hälsan. D-vitamin är ett prohormon som reglerar immunförsvaret och kroppens absorption av kalcium och fosfor. Parodontit är en kronisk inflammatorisk sjukdom som bryter ner tänders stödjevävnad samt käkarnas alveolarben och ger upphov till tandlossning. Denna studie letar i den vetenskapliga litteraturen om det finns kausalitets samband mellan D-vitaminbrist och parodontit eftersom båda tillstånden är skelettala och inflammatoriska sjukdomar. Både parodontit och D-vitaminbrist är vanligt förekommande i den finska befolkningen. Detta arbete är baserat på litteratursökning i PubMed, Melinda, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews och internet hemsidan terveysportti.fi. Litteraturgranskningens resultat är att sambandet mellan D-vitamin halten i serum och parodontal infektion är svag. Populations studier visar att D-vitamin brist har försumbar gynnsam effekt på parodontal infektion. Däremot har D-vitamin i teorin positiv effekt på alveolarbenets mineraldensitet och immunförsvar. Denna studie visar att D-vitaminbrist kan vara orsaken till ett svagt parodontologiskt behandlingssvar om andra starkare parodontologiska riskfaktorer är uteslutna.
  • Costabile, Adele; Bergillos-Meca, Triana; Rasinkangas, Pia; Korpela, Katri; de Vos, Willem M.; Gibson, Glenn R. (2017)
    Background: The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement. Objectives: We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor (TM) Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80 years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics. Results: Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides. L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis. Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas Desulfovibrio decreased also in the L. rhamnosus GG-PB12 combined with SCF group. L. rhamnosus GG combined with SCF reduced total cholesterol and LDL-cholesterol in volunteers with initially elevated concentrations. C-reactive protein significantly decreased during L. rhamnosus GG-PB12 combined with SCF intervention compared to baseline. Conclusion: In conclusion, the synbiotic combination of L. rhamnosus GG with SCF showed a tendency to promote innate immunity by increasing NK cell activity in elderly women and in 70 to 80-year-old volunteers and decreased TC and LDL-c in hyper-cholesterolemic patients. In addition, L. rhamnosus GG-PB12 combined with SCF demonstrated an increase in NK cell activity compared to SCF alone in older volunteers. We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with L. rhamnosus GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.
  • Virtanen, Jenni; Uusitalo, Ruut; Korhonen, Essi M.; Aaltonen, Kirsi; Smura, Teemu; Kuivanen, Suvi; Pakkanen, Sari H.; Mero, Sointu; Patjas, Anu; Riekkinen, Marianna; Kantele, Anu; Nurmi, Visa; Hedman, Klaus; Hepojoki, Jussi; Sironen, Tarja; Huhtamo, Eili; Vapalahti, Olli (2021)
    Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.
  • Ylösmäki, Erkko; Fusciello, Manlio; Martins, Beatriz; Feola, Sara; Hamdan, Firas; Chiaro, Jacopo; Ylösmäki, Leena; Vaughan, Matthew J.; Viitala, Tapani; Kulkarni, Prasad S.; Cerullo, Vincenzo (2021)
    Background Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. Methods Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides. Results Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased. Conclusions This study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform.
  • Strandin, Tomas; Smura, Teemu; Ahola, Paula; Aaltonen, Kirsi; Sironen, Tarja; Hepojoki, Jussi; Eckerle, Isabella; Ulrich, Rainer G.; Vapalahti, Olli; Kipar, Anja; Forbes, Kristian M. (2020)
    Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections in controlled settings. Here we report the isolation, and genetic and phenotypic characterization of a novel Puumala orthohantavirus (PUUV) in cells derived from its reservoir host, the bank vole. The isolation process resulted in cell culture infection that evaded antiviral responses, persisted cell passaging, and had minor viral genome alterations. Critically, experimental infections of bank voles with the new isolate resembled natural infections in terms of viral load and host cell distribution. When compared to an attenuated Vero E6 cell-adapted PUUV Kazan strain, the novel isolate demonstrated delayed virus-specific humoral responses. A lack of virus-specific antibodies was also observed during experimental infections with wild-type PUUV, suggesting that delayed seroconversion could be a general phenomenon during orthohantavirus infection in reservoir hosts. Our results demonstrate that orthohantavirus isolation on cells derived from a vole reservoir host retains wild-type infection properties and should be considered the method of choice for experimental infection models to replicate natural processes.
  • Tuppurainen, E. S. M.; Venter, E. H.; Shisler, J. L.; Gari, G.; Mekonnen, G. A.; Juleff, N.; Lyons, N. A.; De Clercq, K.; Upton, C.; Bowden, T. R.; Babiuk, S.; Babiuk, L. A. (2017)
    Lumpy skin disease, sheeppox and goatpox are high-impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed.
  • Ottman, Noora; Ruokolainen, Lasse; Suomalainen, Alina; Sinkko, Hanna; Karisola, Piia; Lehtimaki, Jenni; Lehto, Maili; Hanski, Ilkka; Alenius, Harri; Fyhrquist, Nanna (2019)
    Background: Sufficient exposure to natural environments, in particular soil and its microbes, has been suggested to be protective against allergies. Objective: We aim at gaining more direct evidence of the environment-microbiota-health axis by studying the colonization of gut microbiota in mice after exposure to soil and by examining immune status in both a steady-state situation and during allergic inflammation. Methods: The gastrointestinal microbiota of mice housed on clean bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing, and the data were combined with immune parameters measured in the gut mucosa, lung tissue, and serum samples. Results: We observed marked differences in the small intestinal and fecal microbiota composition between mice housed on clean bedding or in contact with soil, with a higher proportion of Bacteroidetes relative to Firmicutes in the soil group. The housing environment also influenced mouse intestinal gene expression, as shown by upregulated expression of the immunoregulatory markers IL-10, forkhead box P3, and cytotoxic T lymphocyte-associated protein 4 in the soil group. Importantly, using the murine asthma model, we found that exposure to soil polarizes the immune system toward T(H)1 and a higher level of anti-inflammatory signaling, alleviating T(H)2-ype allergic responses. The inflammatory status of the mice had a marked influence on the composition of the gut microbiota, suggesting bidirectional communication along the gut-lung axis. Conclusion: Our results provide evidence of the role of environmentally acquired microbes in alleviating against T(H)2-driven inflammation, which relates to allergic diseases.
  • Duplouy, Anne; Minard, Guillaume; Saastamoinen, Marjo (2020)
    1. Plant tissues often lack essential nutritive elements and may contain a range of secondary toxic compounds. As nutritional imbalance in food intake may affect the performances of herbivores, the latter have evolved a variety of physiological mechanisms to cope with the challenges of digesting their plant-based diet. Some of these strategies involve living in association with symbiotic microbes that promote the digestion and detoxification of plant compounds or supply their host with essential nutrients missing from the plant diet. In Lepidoptera, a growing body of evidence has, however, recently challenged the idea that herbivores are nutritionally dependent on their gut microbial community. It is suggested that many of the herbivorous Lepidopteran species may not host a resident microbial community, but rather a transient one, acquired from their environment and diet. Studies directly testing these hypotheses are however scarce and come from an even more limited number of species. 2. By coupling comparative metabarcoding, immune gene expression, and metabolomics analyses with experimental manipulation of the gut microbial community of prediapause larvae of the Glanville fritillary butterfly (Melitaea cinxia, L.), we tested whether the gut microbial community supports early larval growth and survival, or modulates metabolism or immunity during early stages of development. 3. We successfully altered this microbiota through antibiotic treatments and consecutively restored it through fecal transplants from conspecifics. Our study suggests that although the microbiota is involved in the up-regulation of an antimicrobial peptide, it did not affect the life history traits or the metabolism of early instars larvae. 4. This study confirms the poor impact of the microbiota on diverse life history traits of yet another Lepidoptera species. However, it also suggests that potential eco-evolutionary host-symbiont strategies that take place in the gut of herbivorous butterfly hosts might have been disregarded, particularly how the microbiota may affect the host immune system homeostasis.
  • Rosa, Elena; van Nouhuys, Saskya; Saastamoinen, Marjo (2017)
    Aggregation can confer advantages in animal foraging, defense, and thermoregulation. There is a tight connection between the evolution of insect sociality and a highly effective immune system, presumably to inhibit rapid disease spread in a crowded environment. This connection is less evident for animals that spend only part of their life cycle in a social environment, such as noneusocial gregarious insects. Our aim was to elucidate the effects of group living by the gregarious larvae of the Glanville fritillary butterfly with respect to individual performance, immunity, and susceptibility to a parasitoid. We were also interested in the role of family relative to common postdiapause environment in shaping life-history traits. Larvae were reared at high or low density and then exposed to the pupal parasitoid wasp Pteromalus apum, either in presence or absence of a previous immune challenge that was used to measure the encapsulation immune response. Surviving adult butterflies were further tested for immunity. The wasp offspring from successfully parasitized butterfly pupae were counted and their brood sex ratios assessed. Larvae reared at high density grew larger and faster than those at low density. Despite high mortality due to parasitism, survival was greater among individuals with high pupal immunity in both density treatments. Moreover, butterfly pupae reared at high density were able to kill a larger fraction of individuals in the parasitoid broods, although this did not increase survival of the host. Finally, a larger proportion of variation observed in most of the traits was explained by butterfly family than by common postdiapause rearing environment, except for adult survival and immunity, for which this pattern was reversed. This gregarious butterfly clearly benefits from high conspecific density in terms of developmental performance and its ability to fight a parasitoid. These positive effects may be driven by cooperative interactions during feeding.
  • Kurki, Karoliina (Helsingin yliopisto, 2021)
    Koin tarpeelliseksi tutustua nimenomaan varsojen immunologiaan, sillä on oleellista erottaa varsojen ja aikuisten hevosten terveydenhoito. Varsojen immuniteetti eroaa aikuisten hevosten immuniteetista muun muassa solutyypeiltään, solujen suhteellisilta määriltään, että solujen tuottamien molekyylien osalta. Varsat kuten muutkin nuoret eläimet usein sairastuvat immunologisesti vahvempia vanhempia eläimiä vakavammin. Varsoja myös kohtaa ensimmäisen muutaman elinvuotensa aikana useampi stressaava elämänvaihe kuten vieroitus, harjoittelun aloittaminen esimerkiksi varsoilla, joista on tarkoitus tehdä ravihevosia, ja monesti myös muutto eri tallille Työssäni käsittelen useita nykyisin käytössä olevia varsoilla käytettäviä hoitomuotoja ja diagnosointitapoja. SNAP-testi on esimerkiksi yleisesti IgG-luokan vasta-aineiden pitoisuuden mittaamiseen käytetty testi, mutta se ei spesifisyydeltään vastaa sitä, mitä luotettavalta diagnoosimenetelmältä odotetaan. Kirjallisuuskatsauksen tuottamaa tietoa voidaan siis hyödyntää esimerkiksi putteellisesta IgG-luokan vasta-aineiden pitoisuuksista kärsivien varsojen hoidossa. On oleellista, että varsa saa ensimmäisen vuorokauden aikana vasta-aineita, sillä noin vuorokauden ikäisellä varsalla suolen epiteeli korvautuu epiteelillä, joka ei enää vasta-aineiden kaltaisia isomolekyylisiä yhdisteitä päästä sisälle. Ternimaidon tärkeyttä varsan hyvinvoinnille ei voi korostaa riittävästi, onhan varsa syntyessään immunokompetentti, mutta immunologisesti naiivi. Tämä tarkoittaa, että varsa tarvitsee immunologisen vasteen muodostukseen emältään saamia vasta-aineita. Vasta-aineita ei hevosella epiteliokoriaalisen istukan takia siirry istukan läpi. Varsa on todella hyvin suojattu kohdunsisäisiltä transplasentaarisilta infektioilta istukan rakenteen ansiosta, mutta koska vasta-aineet eivät pääse sen läpi, täytyy varsan saada ternimaitoa. Varsojen yksi vakavimmista infektiotaudeista on Rhodococcus equi infektio. Kyseessä on bakteeri, joka aiheuttaa vakavaa granulomatoottista pneumoniaa varsoille ja voi levitä muihinkin elinjärjestelmiin kuten silmiin ja niveliin. Tutkin kirjallisuuskatsauksessani, mitä hoitokeinoja tälle infektiolle on ja miten eri hoitokeinot tehoavat. Lisäksi tutkin, olisiko mhdollista kirjallisuuden perusteella rokottaa varsoja tätä tautia vastaan. Varsojen rokottaminen on vaikeaa kuten muidenkin nuorten eläinten, sillä niiden immunologinen vaste eroaa täysikasvuisen eläimen vastaavasta eikä riittävää immuniteettia muodostu. Tämän takia olisi varmaankin tehokkainta rokottaa tammoja jo ennen tiineyttä. Tämäkään vaihtoehto ei ole aina osoittautunut tehokkaaksi.