scholarly journals A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Emilie-Fleur Neubauer ◽  
Angela Z Poole ◽  
Philipp Neubauer ◽  
Olivier Detournay ◽  
Kenneth Tan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune System ◽  
Potential Role ◽  
Early Time ◽  
Innate Immune ◽  
Symbiotic Dinoflagellate ◽  
Aiptasia Pallida ◽  
Time Points ◽  
Colonization Success

The mutualistic endosymbiosis between cnidarians and dinoflagellates is mediated by complex inter-partner signaling events, where the host cnidarian innate immune system plays a crucial role in recognition and regulation of symbionts. To date, little is known about the diversity of thrombospondin-type-1 repeat (TSR) domain proteins in basal metazoans or their potential role in regulation of cnidarian-dinoflagellate mutualisms. We reveal a large and diverse repertoire of TSR proteins in seven anthozoan species, and show that in the model sea anemone Aiptasia pallida the TSR domain promotes colonization of the host by the symbiotic dinoflagellate Symbiodinium minutum. Blocking TSR domains led to decreased colonization success, while adding exogenous TSRs resulted in a ‘super colonization’. Furthermore, gene expression of TSR proteins was highest at early time-points during symbiosis establishment. Our work characterizes the diversity of cnidarian TSR proteins and provides evidence that these proteins play an important role in the establishment of cnidarian-dinoflagellate symbiosis.

scholarly journals The hepatic innate immune response is lobe-specific in a murine model endotoxemia

2019 ◽  
Vol 25 (2) ◽  
pp. 144-154 ◽  
Author(s):  
Leanna Nguyen ◽  
Jeryl Sandoval ◽  
Robyn De Dios ◽  
Elesa Yihdego ◽  
Miguel Zarate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immune Response ◽  
Early Time ◽  
Innate Immune ◽  
Immune Response Gene ◽  
Hepatic Tissue ◽  
Transcriptional Responses ◽  
Time Points ◽  
Lps Challenge

The liver plays a central role in the innate immune response to endotoxemia. While previous studies have demonstrated lobe-specific transcriptional responses to various insults, whether this is true in response to endotoxemia is unknown. We sought to assess whether there were significant intra- and inter-lobe differences in the murine hepatic innate immune transcriptional response to endotoxemia. Adult male ICR mice were exposed to i.p. LPS (5 mg/kg, 30 min, 60 min, 5 h) and primary ( Tnf, Cxcl1, Nfkbia, Tnfiap3) and secondary ( Il6, Nos2) innate immune response gene expression was assessed in the left medial, right medial, left lateral, and right lateral lobes, and the papillary and caudate processes. The expression of all innate immune response genes increased following i.p. LPS challenge. When tested at the early time points (30 and 60 min), the left medial lobe and caudate process consistently demonstrated the highest induction of gene expression. Most inter-lobe differences were attenuated at later time points (5 h). To improve reproducibility of the study of endotoxemia induced by i.p. LPS challenge, inclusion of appropriate methodological details regarding collection of hepatic tissue should be included when reporting scientific results in published manuscripts.

An in vitro transcription analysis of early responses of the human immunodeficiency virus type 1 long terminal repeat to different transcriptional activators

1991 ◽  
Vol 11 (4) ◽  
pp. 1883-1893
Author(s):  
Y C Li ◽  
J Ross ◽  
J A Scheppler ◽  
B R Franza
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein Synthesis ◽  
Early Time ◽  
In Vitro Transcription ◽  
Jurkat Cells ◽  
Time Points ◽  
Immunodeficiency Virus ◽  
Hiv 1

In this report we introduce a simple, fast, and reliable method to prepare whole cell or nuclear extracts from small numbers of cells. These extracts were used to study transcriptional activation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in vitro. Our results revealed that the time courses of activation of extracts derived from cells stimulated with the mitogenic lectin phytohemagglutinin (PHA) or with the tumor promoter phorbol 12-myristate 13-acetate (PMA) are different. PMA induces a rapid onset of increased in vitro transcription from the HIV-1 LTR, while PHA causes a slow and sustained response. The biochemical relevance of protein synthesis inhibition by cycloheximide treatment of cells was investigated. In these studies, PMA induction of a change in in vitro transcriptional activity is not dependent on protein synthesis. Cycloheximide alone is insufficient to induce activation. Oligonucleotide-mediated site-directed mutagenesis demonstrated that mutation of the TATA box in the LTR ablated initiation of both basal-level transcription and activation by extracts from cells stimulated with PMA. Surprisingly, mutation of both kappa B sites in the LTR reduced but did not eliminate the in vitro response to extracts prepared at early time points after PHA or PMA stimulation of Jurkat cells. The reduction was greater in extracts derived from cells treated with PMA. Deletion analysis of the HIV-1 LTR revealed at least one region (-464 to -252) capable of suppressing in vitro transcription in extracts from Jurkat cells stimulated by PMA. This result is consistent with early studies of the HIV-1 LTR in transient transfection assays. We therefore have been able to observe distinct regulatory events at early time points after cells are exposed to agents known to induce transcription of both the HIV-1 LTR reporter gene constructs and the HIV-1 provirus itself.

scholarly journals Gene expression analysis of the innate immune system during early rearing and weaning of meagre (Argyrosomus regius)

2019 ◽  
Vol 94 ◽  
pp. 819-832
Author(s):  
Cindy Campoverde ◽  
Douglas J. Milne ◽  
Christopher J. Secombes ◽  
Alicia Estévez ◽  
Enric Gisbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Expression Analysis ◽  
Innate Immune System ◽  
Gene Expression Analysis ◽  
Innate Immune ◽  
Argyrosomus Regius ◽  
Early Rearing

scholarly journals Candidate innate immune system gene expression in the ecological model Daphnia

2011 ◽  
Vol 35 (10) ◽  
pp. 1068-1077 ◽  
Author(s):  
Ellen Decaestecker ◽  
Pierrick Labbé ◽  
Kirsten Ellegaard ◽  
Judith E. Allen ◽  
Tom J. Little
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Innate Immune System ◽  
Ecological Model ◽  
Innate Immune

scholarly journals Leishmania infection induces a limited differential gene expression in the sand fly midgut

2020 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Late Time ◽  
Time Points

Abstract Background: Phlebotomine sand flies are the vectors of Leishmania worldwide. To develop in the sand fly midgut, Leishmania multiplies and undergoes multiple stage differentiations leading to the infective form, the metacyclic promastigotes. To gain a better understanding of the influence of Leishmania infection on midgut gene expression, we performed RNA-Seq comparing uninfected and Leishmania infantum -infected Lutzomyia longipalpis midguts at seven time points which cover the various Leishmania developmental stages including early time points when blood digestion is taking place, and late time points when the parasites are undergoing metacyclogenesis. Results: Out of over 13,841 transcripts assembled de novo , only 113 sand fly transcripts, about 1%, were differentially expressed. Further, we observed a low overlap of differentially expressed sand fly transcripts across different time points suggesting that each Leishmania stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> -32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 4 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by small fold changes (< 32 fold). The molecular function of these genes has been associated with the metabolism of lipids and detoxification of xenobiotics. Conclusion: Overall, it appears that Leishmania modulates sand fly gene expression early on in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points, where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

scholarly journals Leishmania infection induces a limited differential gene expression in the sand fly midgut

2019 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Lutzomyia Longipalpis ◽  
Late Time ◽  
Blood Digestion ◽  
Time Points

Abstract Background: Phlebotomine sand flies are the vectors of Leishmania worldwide. To develop in the sand fly midgut, Leishmania multiplies and undergoes multiple stage differentiations leading to the infective form, the metacyclic promastigotes. To gain a better understanding of the influence of Leishmania infection in midgut gene expression, we performed RNA-Seq comparing uninfected Lutzomyia longipalpis midguts and Leishmania infantum-infected Lutzomyia longipalpis midguts at seven time points which cover the various developmental Leishmania stages including early time points when blood digestion is taking place and late time points when the parasites are undergoing metacyclogenesis. Results: Out of over 13,841 transcripts assembled de novo, only 113 sand fly transcripts, about 1%, were differentially expressed. Further, we observed a low overlap of differentially expressed sand fly transcripts across different time points suggesting a specific influence of each Leishmania stage on midgut gene expression. Two main patterns of sand fly gene expression modulation were noticed. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> -32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 4 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by small fold changes (< 32 fold), and the molecular function of such genes are associated with the metabolism of lipids and detoxification of xenobiotics (P450). Conclusion: Overall, it appears that Leishmania modulates sand fly gene expression early on in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points, when modest midgut gene expression changes correlate with a massive amount of parasites in the anterior midgut.

scholarly journals RNA Sensor MDA5 Suppresses LINE-1 Retrotransposition By Regulating The Promoter Activity of LINE-1 5’-UTR

2021 ◽  
Author(s):  
Jiaxiu Yan ◽  
Yifei Zhao ◽  
Juan Du ◽  
Yu Wang ◽  
Shaohua Wang ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Promoter Activity ◽  
Feedback Loop ◽  
Innate Immune ◽  
Functional Region ◽  
Protein Levels ◽  
Long Interspersed Elements ◽  
Associated Proteins

Abstract Background: Type 1 long interspersed elements, or LINE-1, are the only active retroelements in human cells. The retrotransposition process of LINE-1 can trigger the activation of the innate immune system and has been proposed to play a role in the development of several autoimmune diseases, including Aicardi-Goutières syndrome (AGS). In contrast, all known AGS-associated proteins, except MDA5, have been reported to affect LINE-1 activity. Thus, MDA5 is likely to also function as a LINE-1 suppressor. Results: MDA5 was found to potently suppress LINE-1 activity in a reporter-based LINE-1 retrotransposition assay. Although MDA5 is an endogenous RNA sensor able to activate the innate immune system, increased interferon (IFN) expression only weakly contributed to MDA5-mediated LINE-1 suppression. Instead, MDA5 effectively reduced the levels of LINE-1 ORF1p and ORF2p, as a result of the MDA5-mediated downregulation of the promoter activity of LINE-1 5’-UTR, and the subsequent generation of LINE-1 RNA. Interestingly, despite MDA5 being a multi-domain protein, the N-terminal 2CARD domain alone is sufficient to inhibit LINE-1 activity. Conclusion: Our data reveal that MDA5 functions as a promoter regulator and suppresses the promoter activity of LINE-1 5’-UTR. Consequently, MDA5 reduces LINE-1 RNA and protein levels, and ultimately inhibits LINE-1 retrotransposition. In contrast, MDA5-induced IFN expression only plays a mild role in MDA5-mediated LINE-1 suppression. In addition, the N-terminal 2CARD domain was found to be a functional region for MDA5 upon inhibition of LINE-1 replication. Thus, our data suggest that besides being an initiator of the innate immune system, MDA5 is also an effector against LINE-1 activity, potentially forming a feedback loop by suppressing LINE-1-induced innate immune activation.

scholarly journals Leishmania infection induces a limited differential gene expression in the sand fly midgut

2020 ◽  
Author(s):  
Iliano V. Coutinho-Abreu ◽  
Tiago D. Serafim ◽  
Claudio Meneses ◽  
Shaden Kamhawi ◽  
Fabiano Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Early Time ◽  
Differentially Expressed ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Developmental Cycle ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Time Points

Abstract Background: Sand flies are the vectors of Leishmania parasites. To develop in the sand fly midgut, Leishmania multiplies and undergoes various stage differentiations giving rise to the infective form, the metacyclic promastigotes. To determine the changes in sand fly midgut gene expression caused by the presence of Leishmania, we performed RNA-Seq of uninfected and Leishmania infantum-infected Lutzomyia longipalpis midguts from seven different libraries corresponding to time points which cover the various Leishmania developmental stages. Results: The combined transcriptomes resulted in the de novo assembly of 13,841 sand fly midgut transcripts. Importantly, only 113 sand fly transcripts, about 1%, were differentially expressed in the presence of Leishmania parasites. Further, we observed distinct differentially expressed sand fly midgut transcripts corresponding to the presence of each of the various Leishmania stages suggesting that each parasite stage influences midgut gene expression in a specific manner. Two main patterns of sand fly gene expression modulation were noted. At early time points (days 1-4), more transcripts were down-regulated by Leishmania infection at large fold changes (> 32 fold). Among the down-regulated genes, the transcription factor Forkhead/HNF-3 and hormone degradation enzymes were differentially regulated on day 2 and appear to be the upstream regulators of nutrient transport, digestive enzymes, and peritrophic matrix proteins. Conversely, at later time points (days 6 onwards), most of the differentially expressed transcripts were up-regulated by Leishmania infection with small fold changes (< 32 fold). The molecular functions of these genes have been associated with the metabolism of lipids and detoxification of xenobiotics. Conclusion: Overall, our data suggest that the presence of Leishmania produces a limited change in the midgut transcript expression profile in sand flies. Further, Leishmania modulates sand fly gene expression early on in the developmental cycle in order to overcome the barriers imposed by the midgut, yet it behaves like a commensal at later time points where a massive number of parasites in the anterior midgut results only in modest changes in midgut gene expression.

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