Comparative genomic analysis of light-regulated transcripts in the Solanaceae

<p>Abstract</p> <p>Background</p> <p>Plants use different light signals to adjust their growth and development to the prevailing environmental conditions. Studies in the model species <it>Arabidopsis thaliana </it>and rice indicate that these adjustments are mediated by large changes in the transcriptome. Here we compared transcriptional responses to light in different species of the Solanaceae to investigate common as well as species-specific changes in gene expression.</p> <p>Results</p> <p>cDNA microarrays were used to identify genes regulated by a transition from long days (LD) to short days (SD) in the leaves of potato and tobacco plants, and by phytochrome B (phyB), the photoreceptor that represses tuberization under LD in potato. We also compared transcriptional responses to photoperiod in <it>Nicotiana tabacum </it>Maryland Mammoth (MM), which flowers only under SD, with those of <it>Nicotiana sylvestris</it>, which flowers only under LD conditions. Finally, we identified genes regulated by red compared to far-red light treatments that promote germination in tomato.</p> <p>Conclusion</p> <p>Most of the genes up-regulated in LD were associated with photosynthesis, the synthesis of protective pigments and the maintenance of redox homeostasis, probably contributing to the acclimatization to seasonal changes in irradiance. Some of the photoperiodically regulated genes were the same in potato and tobacco. Others were different but belonged to similar functional categories, suggesting that conserved as well as convergent evolutionary processes are responsible for physiological adjustments to seasonal changes in the Solanaceae. A β-ZIP transcription factor whose expression correlated with the floral transition in <it>Nicotiana </it>species with contrasting photoperiodic responses was also regulated by photoperiod and phyB in potato, and is a candidate gene to act as a general regulator of photoperiodic responses. Finally, <it>GIGANTEA</it>, a gene that controls flowering time in <it>Arabidopsis thaliana </it>and rice, was regulated by photoperiod in the leaves of potato and tobacco and by red compared to far-light treatments that promote germination in tomato seeds, suggesting that a conserved light signaling cascade acts across developmental contexts and species.</p

TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung

We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3 +/+ ) and TLR3 gene-deficient (TLR3 −/− ) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni -sensitized TLR3 +/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3 −/− mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3 +/+ mice. Macrophages from TLR3 −/− mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4 + CD25 + T cells were present in the lungs of TLR3 −/− mice compared with TLR3 +/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3 −/− mice released significantly higher levels of IL-17 levels relative to TLR3 +/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61443/1/3436_ftp.pd

Filarial Lymphedema Is Characterized by Antigen- Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Methods and Findings: To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-c and TNF-a—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFb, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls. Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema

Schistosome Eggs Impair Protective Th1/Th17 Immune Responses Against Salmonella Infection

Countries with a high incidence of helminth infections are characterized by high morbidity and mortality to infections with intracellular pathogens such as Salmonella. Some patients with Salmonella-Schistosoma co-infections develop a so-called "chronic septicemic salmonellosis," with prolonged fever and enlargement of the liver and spleen. These effects are most likely due to the overall immunoregulatory activities of schistosomes such as induction of Tregs, Bregs, alternatively activated macrophages, and degradation of antibodies. However, detailed underlying mechanisms are not very well investigated. Here, we show that intraperitoneal application of live Schistosoma mansoni eggs prior to infection with Salmonella Typhimurium in mice leads to an impairment of IFN-γ and IL-17 responses together with a higher bacterial load compared to Salmonella infection alone. S. mansoni eggs were found in granulomas in the visceral peritoneum attached to the colon. Immunohistological staining revealed IPSE/alpha-1, a glycoprotein secreted from live schistosome eggs, and recruited basophils around the eggs. Noteworthy, IPSE/alpha-1 is known to trigger IL-4 and IL-13 release from basophils which in turn is known to suppress Th1/Th17 responses. Therefore, our data support a mechanism of how schistosomes impair a protective immune response against Salmonella infection and increase our understanding of helminth-bacterial co-infections

Circulating cytokine levels and antibody responses to human Schistosoma haematobium: IL-5 and IL-10 levels depend upon age and infection status

Experimental schistosome infections induce strong parasite-specific Th2 responses. This study aims to relate human systemic cytokine and antibody levels to schistosome infection levels and history. Levels of anti-Schistosoma haematobium antibodies (directed against crude cercariae, egg and adult worm antigens) and plasma cytokines (IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-21, and IL-23) were measured by ELISA in 227 Zimbabweans (6–60 years old) in a schistosome-endemic area and related to age and infection status. Egg-positive people had significantly higher levels of specific antibodies, IL-2, IFN-γ and IL-23. In contrast, egg-negative individuals had significantly higher circulating IL-10, IL-4, IL-13 and IL-21 that were detected with high frequency in all participants. Subjects with detectable plasma IL-17 produced few or no eggs. When analyzed by age, IL-4 and IL-10 increased significantly, as did schistosome-specific antibodies. However, when age was combined with infection status, IL-5 declined over time in egg-positive people, while increased with age in the egg-negative group. Older, lifelong residents had significantly higher IL-4 and IL-5 levels than younger egg-negative people. Thus, a mixed Th1/Th2 systemic environment occurs in people with patent schistosome infection, while a stronger Th2-dominated suite of cytokines is evident in egg-negative individuals

Serum levels of cytokines in water buffaloes experimentally infected with Fasciola gigantica

Fasciola gigantica infection in water buffaloes causes significant economic losses especially 27 in developing countries. Although modulation of the host immune response by cytokine 28 neutralization or vaccination is a promising approach to control infection with this parasite, our 29 understanding of cytokine's dynamic during F. gigantica infection is limited. To address this, 30 we quantified the levels of serum cytokines produced in water buffaloes following experimental 31 infection with F. gigantica. Five buffaloes were infected via oral gavage with 500 viable F. 32 gigantica metacercariae and blood samples were collected from buffaloes one week before 33 infection and for 13 consecutive weeks thereafter. The levels of 10 cytokines in serum samples 34 were simultaneously determined using ELISA. F. gigantica failed to elicit the production of 35 various pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-12, and 36 IFN-γ. On the other hand, evidence of a Th2 type response was detected, but only early in the 37 course of parasite colonization and included modest increase in the levels of IL-10 and IL-13. 38 The results also revealed suppression of the immune responses as a feature of chronic F. 39 gigantica infection in buffaloes. Taken together, F. gigantica seems to elicit a modest Th2 40 response at early stage of infection in order to downregulate harmful Th1- and Th17-type 41 inflammatory responses in experimentally infected buffaloes. The full extent of anti-F. 42 gigantica immune response and its relation to pathogenesis requires further study

Regulation of pathogenesis and immunity in helminth infections

Helminths are multicellular eukaryotic parasites that infect over one quarter of the world’s population. Through coevolution with the human immune system, these organisms have learned to exploit immunoregulatory pathways, resulting in asymptomatic tolerance of infections in many individuals. When infections and the resulting immune responses become dysregulated, however, acute and chronic pathologies often develop. A recent international meeting focused on how these parasites modulate host immunity and how control of parasitic and immunopathological disease might be achieved

CD11c depletion severely disrupts Th2 induction and development in vivo

Although dendritic cells (DCs) are adept initiators of CD4+ T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c–diphtheria toxin (DTx) receptor mice to deplete CD11c+ cells during the priming stage of the CD4+ Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c+ DCs from all tissues tested, with 70–80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4+ T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c+ antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines

Transcriptional Regulation of T Helper 17 Cell Differentiation

The third lineage of T helper subsets, Th17, has recently been identified as an IL-17-producing CD4+ Th cell, and its functions and regulatory mechanisms have been extensively characterized in immune responses. Functional studies have provided evidence that Th17 cells are important for the modulation of autoimmune responses, such as chronic asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. Murine Th17 cell differentiation is enhanced by the coordinated functions of distinct cytokines including TGFβ, IL-6, IL-21, and IL-23, whereas IL-2, IL-4, IFNγ, and IL-27 inhibit its differentiation. In addition, Th17 cells are controlled by several transcription factors such as RORγ t, IRF4, BATF, FoxP3, T-bet, PPARγ, E-FABP, and SOCSs. This review focuses on the functions and regulatory mechanisms of several transcription factors in the control of Th17 cell differentiation

Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases