scholarly journals Analysis of the basal colonic innate immune response of pigs divergent in feed efficiency and following an ex vivo lipopolysaccharide challenge

2019 ◽  
Vol 51 (9) ◽  
pp. 443-448 ◽  
Author(s):  
Stafford Vigors ◽  
John V. O’ Doherty ◽  
Marion Ryan ◽  
Torres Sweeney
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Feed Efficiency ◽  
Ex Vivo ◽  
Innate Immune ◽  
Colonic Tissue ◽  
Experimental Conditions ◽  
Defense Proteins ◽  
Lps Challenge ◽  
Genes Encoding

While feed efficiency is influenced by multiple physiological processes, it is not known how efficient and inefficient pigs differ in relation to their basal immune response, and particularly their innate immune response to a microbial challenge. Hence, the objective was to examine the expression of genes encoding innate immune response markers in basal colonic tissue and colonic tissue following an ex vivo lipopolysaccharide (LPS) challenge from pigs divergent in residual feed intake (RFI). Pigs that differed in RFI were selected from two different farms of origin. Colonic tissue was harvested from high RFI (HRFI) and low (LRFI) pigs, and two experimental conditions were explored: the first was basal unchallenged tissue and the second was colonic tissue following an ex vivo LPS challenge. RNA was extracted and tested on a Nanostring panel of 72 genes coding for barrier defense proteins, transmembrane receptors, kinases, transcription regulators, cytokines, and cytokine regulators. In the basal unchallenged tissue, the LRFI pigs had increased expression of AOAH, AP1, and TRAM and the cytokines TNF, IL10, and CXCL8, compared with the HRFI pigs ( P < 0.05), with a significant effect of farm of origin on 31 genes ( P < 0.05). In the LPS-challenged tissues, the LRFI group had higher expression of TLR1, TLR7, TLR8, GPR43/FFAR2, JAK2, and NFAM1 compared with the HRFI group ( P < 0.05). In conclusion, these data suggest that LRFI pigs have an upregulated basal colonic inflammatory state and a heightened response to an LPS challenge compared with the inefficient HRFI pigs. This immune profile potentially enhances their capacity to respond to an infectious challenge.

High content screening and computational prediction reveal viral genes that suppress innate immune response

2021 ◽  
Author(s):  
Tai L Ng ◽  
Erika J Olson ◽  
Tae Yeon Yoo ◽  
H. Sloane Weiss ◽  
Yukiye Koide ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Nuclear Transport ◽  
Computational Prediction ◽  
Viral Proteins ◽  
Innate Immune ◽  
Type I ◽  
Viral Genes ◽  
Genes Encoding

Suppression of the host innate immune response is a critical aspect of viral replication. Upon infection, viruses may introduce one or more proteins that inhibit key immune pathways, such as the type I interferon pathway. However, the ability to predict and evaluate viral protein bioactivity on targeted pathways remains challenging and is typically done on a single virus/gene basis. Here, we present a medium-throughput high-content cell-based assay to reveal the immunosuppressive effects of viral proteins. To test the predictive power of our approach, we developed a library of 800 genes encoding known, predicted, and uncharacterized human viral genes. We find that previously known immune suppressors from numerous viral families such as Picornaviridae and Flaviviridae recorded positive responses. These include a number of viral proteases for which we further confirmed that innate immune suppression depends on protease activity. A class of predicted inhibitors encoded by Rhabdoviridae viruses was demonstrated to block nuclear transport, and several previously uncharacterized proteins from uncultivated viruses were shown to inhibit nuclear transport of the transcription factors NF-kB and IRF3. We propose that this pathway-based assay, together with early sequencing, gene synthesis, and viral infection studies, could partly serve as the basis for rapid in vitro characterization of novel viral proteins.

scholarly journals In utero heat stress alters the postnatal innate immune response of pigs

2020 ◽  
Vol 98 (12) ◽  
Author(s):  
Jay S Johnson ◽  
Jacob M Maskal ◽  
Alan W Duttlinger ◽  
Kouassi R Kpodo ◽  
Betty R McConn ◽  
...  
Keyword(s):  
Immune Response ◽  
Heat Stress ◽  
Stress Response ◽  
Body Temperature ◽  
Innate Immune Response ◽  
In Utero ◽  
Innate Immune ◽  
Postnatal Life ◽  
Lps Challenge ◽  
Cell Counts

Abstract The effects of in utero heat stress (IUHS) range from decreased growth performance to altered behavior, but the long-term impact of IUHS on postnatal innate immune function in pigs is unknown. Therefore, the study objective was to determine the effects of early gestation IUHS on the immune, metabolic, and stress response of pigs subjected to an 8 hr lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1 °C) or heat stress (HS; n = 12; cyclic 26 to 36 °C) conditions from days 6 to 59 of gestation, and then TN conditions (20.9 ± 2.3 °C) from day 60 of gestation to farrowing. At 12 wk of age, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW mixed with sterile saline [SAL] and injected at 2 µL/kg BW) or SAL (2 µL/kg BW). Body temperature was monitored every 30 min, and blood was obtained at 0, 1, 2, 3, 4, 6, and 8 hr following the LPS challenge. Blood samples were analyzed for glucose, insulin, non-esterified fatty acids (NEFA), cortisol, and cytokine concentrations. In addition, white blood cell counts were determined at 0 and 4 hr. Hour 0 data were used as covariates. Body temperature was increased (P &lt; 0.01) in LPS (40.88 ± 0.08 °C) vs. SAL (39.83 ± 0.08 °C) pigs. Eosinophils tended to be decreased overall (P = 0.09; 43.9%) in IUHS vs. IUTN pigs. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS vs. IUTN pigs. The NEFA concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs tended to have greater (127.4%) circulating NEFA concentrations compared with IUTN-SAL and IUHS-SAL pigs. Cortisol was increased (P = 0.04) in IUHS-LPS compared with IUTN-LPS pigs at 3 hr (21.5%) and 4 hr (64.3%). At 1 hr, tumor necrosis factor α was increased (P = 0.01; 115.1%) in IUHS-LPS compared with IUTN-LPS pigs. Overall, interleukin-1β (IL-1β) and interleukin-6 (IL-6) were greater (P &lt; 0.04; 281.3% and 297.8%, respectively) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs had increased IL-1β and IL-6 concentrations compared with IUTN-SAL and IUHS-SAL pigs. In summary, IUHS altered the postnatal cytokine, metabolic, and physiological stress response of pigs during postnatal life, which may have negative implications toward the innate immune response of IUHS pigs to pathogens.

The Role of Hox Proteins and Interferon Regulatory Factors in Myeloid Differentiation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. sci-34-sci-34
Author(s):  
Elizabeth A. Eklund
Keyword(s):  
Immune Response ◽  
Transcription Factors ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Gene Encoding ◽  
Hox Proteins ◽  
Regulatory Factors ◽  
Interferon Regulatory Factors ◽  
Genes Encoding ◽  
Myeloid Progenitors

During myelopoiesis, differentiating phagocytes develop functional competence and undergo proliferation arrest and eventual programmed cell death. This process involves transcriptional regulation of genes which mediate the innate immune response, mitotic arrest, and apoptosis. A number of transcription factor families play important roles in regulating such genes, including Hox proteins and interferon regulatory factors (IRFs). Disordered expression of Hox proteins is associated with myeloid leukemogenesis. Hox proteins are homeodomain transcription factors that are organized in four paralog groups (A–D). Expression of HoxA7-11 (the ABD-HOXA genes) is characteristic of myeloid progenitors. ABD-HOXA transcription decreases with CD34+ to CD34− progression, and persistent expression of these genes is found in poor prognosis leukemia. Abd Hox proteins regulate genes that are involved in multiple aspects of myelopoiesis. For example, HoxA10 represses transcription of the genes encoding gp91phox and p67phox in myeloid progenitors (the CYBB and NCF2 genes, respectively). In contrast, HoxA9 activates transcription of these genes as differentiation proceeds. Since these are the rate-limiting NADPH oxidase components, HoxA proteins influence the innate immune response. HoxA10 activates transcription of the gene encoding Beta3 integrin, thereby further facilitating NADPH oxidase activation and influencing adhesion. HoxA10 also activates transcription of DUSP4, the gene encoding MAP kinase phosphatase 2 (Mkp2). Mkp2 antagonizes the activity of c-Jun N-terminal kinases (Jnk). Since HoxA10-activation of DUSP4 decreases during myelopoiesis, decreased Mkp2 expression in mature phagocytes facilitates apoptosis via Jnk. Interferon regulatory factors (IRF) also regulate multiple aspects of myelopoiesis. IRF1 and ICSBP/IRF8 activate transcription of the CYBB and NCF2 genes in cooperation with the ets protein PU.1. ICSBP/IRF8 also contributes to phagocyte function by activating genes encoding TLR4, IL12, and Nramp. Additionally, IRF proteins regulate cell cycle progression and proliferation. IRF2, ICSBP/IRF8, and PU.1 activate transcription of gene encoding Neurofibromin 1, thereby downregulating the proliferative response to cytokines such as GM-CSF, M-CSF, and G-CSF. ICSBP/IRF8 and PU.1 also activate the gene encoding Ink4b, thereby also influencing proliferation. In myeloid progenitors, ICSBP/IRF8 influences cell survival by repressing transcription of PTPN13, the gene encoding Fas-associated phosphatase 1 (Fap1), a Fas-antagonist. Decreased ICSBP/IRF8-induced PTPN13 repression during myelopoiesis increases susceptibility of mature phagocytes to Fas-induced apoptosis. Such studies reveal that multiple aspects of myelopoiesis are regulated by common sets of transcription factors. This may suggest therapeutic targets for myeloid leukemias or other disorders of myeloid development.

The Innate Immune Response, Clinical Outcomes, and Ex Vivo HCV Antiviral Efficacy of a TLR7 Agonist (PF-4878691)

2011 ◽  
Vol 89 (6) ◽  
pp. 821-829 ◽  
Author(s):  
M D Fidock ◽  
B E Souberbielle ◽  
C Laxton ◽  
J Rawal ◽  
O Delpuech-Adams ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Innate Immune Response ◽  
Ex Vivo ◽  
Innate Immune ◽  
Antiviral Efficacy ◽  
Tlr7 Agonist

Induction of innate immune response in fresh human lung tissue ex vivo following P. aeruginosa infection

2018 ◽  
Author(s):  
Laura Mueller ◽  
Nadine Kraemer ◽  
Peter Braubach ◽  
Danny Jonigk ◽  
Hans-Gerd Fieguth ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
Innate Immune ◽  
Human Lung Tissue

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.

scholarly journals Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system

2003 ◽  
Vol 162 (2) ◽  
pp. 257-268 ◽  
Author(s):  
Denis Soulet ◽  
Serge Rivest
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Innate Immune Response ◽  
Transcriptional Activation ◽  
Critical Role ◽  
Innate Immune ◽  
Genes Encoding ◽  
Factor Α ◽  
Mouse Central Nervous System

The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor α and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.

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