scholarly journals The Importance of Interferon-Tau in the Diagnosis of Pregnancy

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Alicja Kowalczyk ◽  
Ewa Czerniawska-Piątkowska ◽  
Marcjanna Wrzecińska
Keyword(s):  
Dairy Cattle ◽  
Specific Protein ◽  
Type I ◽  
Reproductive Disorders ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Genes Encoding ◽  
Pregnancy Status ◽  
New Type ◽  
Pregnancy Recognition

Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2–3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.

scholarly journals RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice

2016 ◽  
Vol 213 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Vladislav Pokatayev ◽  
Naushaba Hasin ◽  
Hyongi Chon ◽  
Susana M. Cerritelli ◽  
Kiran Sakhuja ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Ventral Surface ◽  
Type I ◽  
Catalytic Core ◽  
Interferon Stimulated Genes ◽  
Early Embryonic Lethality ◽  
Genes Encoding ◽  
Immune Sensing ◽  
Rnase H2 ◽  
Innate Immune Sensing

The neuroinflammatory autoimmune disease Aicardi-Goutières syndrome (AGS) develops from mutations in genes encoding several nucleotide-processing proteins, including RNase H2. Defective RNase H2 may induce accumulation of self-nucleic acid species that trigger chronic type I interferon and inflammatory responses, leading to AGS pathology. We created a knock-in mouse model with an RNase H2 AGS mutation in a highly conserved residue of the catalytic subunit, Rnaseh2aG37S/G37S (G37S), to understand disease pathology. G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice. Importantly, we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS–STING signaling pathway. Ablation of STING in the G37S mice results in partial rescue of the perinatal lethality, with viable mice exhibiting white spotting on their ventral surface. We believe that the G37S knock-in mouse provides an excellent animal model for studying RNASEH2-associated autoimmune diseases.

scholarly journals Identification of new type I interferon-stimulated genes and investigation of their involvement in IFN-β activation

2018 ◽  
Vol 9 (9) ◽  
pp. 799-807 ◽  
Author(s):  
Xiaolin Zhang ◽  
Wei Yang ◽  
Xinlu Wang ◽  
Xuyuan Zhang ◽  
Huabin Tian ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
New Type

scholarly journals Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau

2012 ◽  
Vol 44 (16) ◽  
pp. 799-810 ◽  
Author(s):  
N. Forde ◽  
G. B. Duffy ◽  
P. A. McGettigan ◽  
J. A. Browne ◽  
J. P. Mehta ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Transcriptional Response ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Short Term Exposure ◽  
Pregnancy Status ◽  
In Vivo Analysis

The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endometria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h ( P < 0.05). On day 13 following estrous endometrial expression of nine genes increased [ ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven genes decreased ( SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, MGC128929, and WBSCR17; P < 0.05) in pregnant compared with cyclic heifers. Of these DEGs, significant differences in expression between pregnant and cyclic endometria were maintained on day 16 for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, and ZSWIM4 ( P < 0.05) both their expression was not directly regulated by IFNT in vivo. Analysis of the expression of selected interferon-stimulated genes in blood samples from postpartum dairy cows revealed a significant increase ( P < 0.05) in expression of ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared with cyclic controls. In conclusion, RNAseq identified a number of novel pregnancy-associated genes in the endometrium of cattle during early pregnancy that are not regulated by IFNT in vivo. In addition, a number of genes that are directly regulated by short term exposure to IFNT in vivo are differentially expressed on day 18 following estrus detection in the blood of postpartum dairy cows depending on their pregnancy status.

scholarly journals LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host

2010 ◽  
Vol 78 (11) ◽  
pp. 4705-4713 ◽  
Author(s):  
Hesham F. Nawar ◽  
Natalie D. King-Lyons ◽  
John C. Hu ◽  
Raymond C. Pasek ◽  
Terry D. Connell
Keyword(s):  
Escherichia Coli ◽  
Coli Strain ◽  
Amino Acid Sequences ◽  
Type I ◽  
Avian Host ◽  
Type Ii ◽  
E Coli ◽  
Heat Labile ◽  
Genes Encoding ◽  
New Type

ABSTRACT Two families of bacterial heat-labile enterotoxins (HLTs) have been described: the type I HLTs are comprised of cholera toxin (CT) of Vibrio cholerae, LT-I of Escherichia coli, and several related HLTs; the type II HLTs are comprised of LT-IIa and LT-IIb. Herein, we report LT-IIc, a new type II HLT encoded from an enterotoxigenic E. coli (ETEC) strain isolated from an avian host. Using a mouse Y1 adrenal cell bioassay, LT-IIc was shown to be less cytotoxic than CT, LT-IIa, or LT-IIb. Cytotoxicity of LT-IIc was partially neutralized by antisera recognizing LT-IIa or LT-IIb but not by anti-CT antiserum. Genes encoding putative A polypeptide and B polypeptides of LT-IIc were arranged in an operon which was flanked by potential prophage sequences. Analysis of the nucleotide and predicted amino acid sequences demonstrated that the A polypeptide of LT-IIc has moderate homology to the A polypeptides of CT and LT-I and high homology to the A polypeptides of LT-IIa and LT-IIb. The B polypeptide of LT-IIc exhibited no significant homology to the B polypeptides of CT and LT-I and only moderate homology to the B polypeptides of LT-IIa and LT-IIb. The binding pattern of LT-IIc for gangliosides was distinctive from that of either LT-IIa or LT-IIb. The data suggest that other types of the type II HLT subfamily are circulating in the environment and that host specificity of type II HLT is likely governed by changes in the B polypeptide which mediate binding to receptors.

scholarly journals Paracrine and endocrine actions of interferon tau (IFNT)

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F45-F59 ◽  
Author(s):  
Thomas R Hansen ◽  
Leticia D P Sinedino ◽  
Thomas E Spencer
Keyword(s):  
Mononuclear Cells ◽  
Endocrine Effects ◽  
Interferon Tau ◽  
Peripheral Blood Mononuclear ◽  
Prostaglandin F2 Alpha ◽  
Oxytocin Receptors ◽  
Specific Manner ◽  
Pregnancy Status ◽  
A Cell ◽  
Pregnancy Recognition

This review focuses on the paracrine and endocrine actions of interferon tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants.

scholarly journals Interferon-tau and fertility in ruminants

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F33-F43 ◽  
Author(s):  
N Forde ◽  
P Lonergan
Keyword(s):  
Prostaglandin F2α ◽  
Threshold Level ◽  
Type I ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Domestic Ruminants ◽  
Oxytocin Receptors ◽  
Pregnancy Recognition ◽  
Maternal Recognition Of Pregnancy ◽  
Primary Agent

Establishment of pregnancy in domestic ruminants includes pregnancy recognition signalling by the conceptus, implantation and placentation. Despite the high fertilisation success rate in ruminants, a significant amount of embryo loss occurs, primarily during early gestation. Interferon-tau (IFNT), a type I interferon that is exclusively secreted by the cells of the trophectoderm of the ruminant conceptus, has been recognised as the primary agent for maternal recognition of pregnancy in ruminants. It produces its antiluteolytic effect on the corpus luteum by inhibiting the expression of oxytocin receptors in the uterine epithelial cells, which prevents pulsatile, luteolytic secretion of prostaglandin F2α by the uterine endometrium. While the importance of IFNT in maternal recognition of pregnancy and prevention of luteolysis in ruminants is unequivocal, important questions, for example, relating to the threshold level of IFNT required for pregnancy maintenance, remain unanswered. This paper reviews data linking IFNT with measures of fertility in ruminants.

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

Gelatin-Containing Vaccines for Varicella, Zoster, Measles, Mumps, and Rubella Induce Basophil Activation in Patients with Alpha-Gal Syndrome

2021 ◽  
pp. 1-7
Author(s):  
Paul Schmidle ◽  
Jana Mehlich ◽  
Knut Brockow ◽  
Ulf Darsow ◽  
Tilo Biedermann ◽  
...  
Keyword(s):  
Case Reports ◽  
Meat Products ◽  
Live Vaccine ◽  
Basophil Activation ◽  
Type I ◽  
Mmr Vaccine ◽  
Varicella Zoster ◽  
Additional Tool ◽  
Severe Anaphylaxis ◽  
New Type

Background: The alpha-gal syndrome (AGS) describes a new type I allergy entity to the carbohydrate epitope galactose-α-1,3-galactose (alpha-gal), which is mainly found in mammalian food products (e.g., beef, pork, and venison). Apart from meat products, alpha-gal can also be found in products containing gelatin of bovine or porcine origin. Recent case reports pointed to severe anaphylaxis in patients suffering from AGS after vaccination with vaccines containing hydrolyzed gelatin. It was the objective of this study to evaluate if basophil activation tests (BATs) performed with such vaccines were positive in patients with AGS. Methods: BAT was performed with different dilutions of a gelatin-containing measles, mumps, and rubella (MMR) live vaccine; an attenuated varicella (V) vaccine; an attenuated V-zoster (VZ) vaccine; a MMR live vaccine not containing gelatin (non-gelatin MMR vaccine) in 2 patients with confirmed AGS, 2 patients highly suspicious for AGS, and 2 healthy individuals without any previous medical history for allergies. Results: All patients showed strongly positive results for all gelatin-containing vaccines (MMR vaccine, V vaccine, and VZ vaccine). Non-gelatin MMR vaccine was negative. The 2 healthy controls did not show any basophil activation. Conclusions: Gelatin-containing vaccines should be administered with caution or avoided in patients with AGS because of their high potential to activate basophils indicating a risk for anaphylaxis. Also, BAT is a useful additional tool when it comes to screening for potentially high-risk alpha-gal-containing drugs.

scholarly journals POS0611 THE EFFECT OF RITUXIMAB BIOSIMILAR THERAPY ON THE EXPRESSION OF INTERFERON-STIMULATED GENES (“INTERFERON SIGNATURE”) IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Signature ◽  
Response To Therapy ◽  
Type I Interferons ◽  
Control Group ◽  
Type I ◽  
Acute Phase Reactants ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Healthy Donors

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared

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