scholarly journals Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird

2020 ◽  
Vol 37 (6) ◽  
pp. 1708-1726
Author(s):  
Hila Levy ◽  
Steven R Fiddaman ◽  
Juliana A Vianna ◽  
Daly Noll ◽  
Gemma V Clucas ◽  
...  
Keyword(s):  
Geographic Range ◽  
Gentoo Penguin ◽  
Innate Immune ◽  
Evolutionary Time ◽  
Immune Genes ◽  
Changing Environments ◽  
Pathogen Challenge ◽  
Innate Immune Genes ◽  
Latitudinal Range

Abstract Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes—the Toll-like receptors (TLRs)—across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world’s most rapidly changing environments.

Flagellin induces innate immune genes in bronchial epithelial cells in vivo: Role of TET2

2021 ◽  
Author(s):  
Wanhai Qin ◽  
Xanthe Brands ◽  
Cornelis Veer ◽  
Alex F. Vos ◽  
Brendon P. Scicluna ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Bronchial Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

scholarly journals The role of coagulation factors VII, VIII, and IX on the tropism and inflammatory effect of Adenovector on liver and breast cell lines

2021 ◽  
Author(s):  
Rozita Ghojoghi ◽  
Fatemeh Nekooei ◽  
Fatemeh Vatanparast ◽  
Jamal Srv ◽  
Ali-Mohammad Tamaddon ◽  
...  
Keyword(s):  
Cell Lines ◽  
Fluorescent Microscopy ◽  
Coagulation Factors ◽  
Innate Immune ◽  
P Value ◽  
Target Cells ◽  
Potential Measurement ◽  
Immune Genes ◽  
Innate Immune Genes

Abstract Introduction: Adenovectors are promising vectors for gene delivery to the target cells. During gene therapy, AdV interact with plasma components particularly vitamin K-dependent coagulation factors. In this study, we analyzed the comparison between cell entrance, inflammatory patterns, and innate immune induction which induced by the Adenoventor and Adenovector coated by FVII, FVIII, and FIX on two cell-lines; HepG2, MCF7. Methods: The Adenovector expressing GFP (AdVGFP) was prepared and then loading of AdV by coagulation factors were analyzed by zeta potential measurement. The non-toxic MOI of vector employed alone or in complex with coagulation factors VII, FVIII, and FIX applied on HepG2 and MCF7 cell lines. The transduction rates of complexes were analyzed by fluorescent microscopy and flow cytometry. The expression levels of innate immune genes (PKR, STING, IRF-3 and MX-1) were measured by Real-time PCR. Also the level of IL-6 and IL-1β were evaluated by using ELISA assay. Results: The loading of Adenovector by FVII and FIX decreased the zeta charge of the complex particles and enhanced the entry rate in both HepG2 (FVII/AdV: 38.3% and FIX/AdV: 61.9%) and MCF7 (FVII/AdV: 31.2% and FIX/AdV: 36.6%). The expression of IL-6 cytokine enhanced when AdV exposed to FVII (P value: 0.005) in MCF7 and also FVII (P value: 0.01) and FIX (P value: 0.009) in HepG2. Adenovector coated by FVII and FIX could significantly alter the expression pattern of innate immune genes. Conclusion: The findings are highlighted the role of FVII and in particular FIX in facilitating the entry of vector into the cells; also they are enhanced the inflammation and innate immune responses. Interestingly, FVIII had no effect or even adverse effect on entry, inflammation, and innate immune induction.

scholarly journals Human Papillomavirus 16 E6 and E7 Synergistically Repress Innate Immune Gene Transcription

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Claire D. James ◽  
Christian T. Fontan ◽  
Raymonde Otoa ◽  
Dipon Das ◽  
Apurva T. Prabhakar ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Innate Immune ◽  
Cellular Growth ◽  
Immune Gene ◽  
Human Papillomavirus 16 ◽  
Immune Genes ◽  
Hpv16 Genome ◽  
E6 And E7 ◽  
Innate Immune Genes

ABSTRACT Human papillomaviruses (HPV) are causative agents in 5% of all cancers, including the majority of anogenital and oropharyngeal cancers. Downregulation of innate immune genes (IIGs) by HPV to promote the viral life cycle is well documented; E6 and E7 are known repressors of these genes. More recently, we demonstrated that E2 could also repress IIGs. These studies have been carried out in cells overexpressing the viral proteins, and to further investigate the role of individual viral proteins in this repression, we introduced stop codons into E6 and/or E7 in the entire HPV16 genome and generated N/Tert-1 cells stably maintaining the HPV16 genomes. We demonstrate that E6 or E7 individually is not sufficient to repress IIG expression in the context of the entire HPV16 genome; both are required for a synergistic repression. The DNA damage response (DDR) is activated by HPV16 irrespective of E6 and E7 expression, presumably due to viral replication; E1 is a known activator of the DDR. In addition, replication stress was apparent in HPV16-positive cells lacking E6 and E7, manifested by attenuated cellular growth and activation of replication stress genes. These studies led us to the following model. Viral replication per se can activate the DDR following infection, and this activation is a known inducer of IIG expression, which may induce cellular senescence. To combat this, E6 and E7 synergistically combine to manipulate the DDR and actively repress innate immune gene expression promoting cellular growth; neither protein by itself is able to do this. IMPORTANCE The role of human papillomavirus 16 (HPV16) in human cancers is well established; however, to date there are no antiviral therapeutics that are available for combatting these cancers. To identify such targets, we must enhance the understanding of the viral life cycle. Innate immune genes (IIGs) are repressed by HPV16, and we have reported that this repression persists through to cancer. Reversal of this repression would boost the immune response to HPV16-positive tumors, an area that is becoming more important given the advances in immunotherapy. This report demonstrates that E6 and E7 synergistically repress IIG expression in the context of the entire HPV16 genome. Removal of either protein activates the expression of IIGs by HPV16. Therefore, gaining a precise understanding of how the viral oncogenes repress IIG expression represents an opportunity to reverse this repression and boost the immune response to HPV16 infections for therapeutic gain.

scholarly journals Human papillomavirus 16 E6 and E7 synergistically repress innate immune gene transcription

2019 ◽  
Author(s):  
Claire D. James ◽  
Christian T. Fontan ◽  
Raymonde Otoa ◽  
Dipon Das ◽  
Apurva T. Prabhakar ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Innate Immune ◽  
Cellular Growth ◽  
Immune Gene ◽  
Immune Genes ◽  
Hpv16 Genome ◽  
E6 And E7 ◽  
Innate Immune Genes ◽  
Innate Immune Gene

AbstractHuman papillomaviruses are causative agents in 5% of all cancers, including the majority of anogenital and oropharyngeal cancers. Downregulation of innate immune genes (IIGs) by HPV to promote the viral life cycle is well documented; E6 and E7 are known repressors of these genes. More recently we demonstrated that E2 could also repress IIGs. These studies have been carried out in cells over-expressing the viral proteins and to further investigate the role of individual viral proteins in this repression we introduced stop codons into E6 and/or E7 in the entire HPV16 genome and generated N/Tert-1 cells stably maintaining the HPV16 genomes. We demonstrate that E6 or E7 individually are not sufficient to repress IIG expression in the context of the entire HPV16 genome, both are required for a synergistic repression. The DNA damage response (DDR) is activated by HPV16 irrespective of E6 and E7 expression, presumably due to viral replication; E1 is a known activator of the DDR. In addition, replication stress was apparent in the HPV16 positive cells lacking E6 and E7, manifested by attenuated cellular growth and activation of replication stress genes. These studies lead us to the following model. Viral replication per se can activate the DDR following infection, and this activation is a known inducer of IIG expression which could induce cellular senescence. To combat this, E6 and E7 synergistically combine to manipulate the DDR and actively repress innate immune gene expression promoting cellular growth; neither protein by itself is able to do this.ImportanceThe role of HPV16 in human cancers is well established; however, to date there are no anti-viral therapeutics that are available for combatting these cancers. To identify such targets, we must enhance understanding of the viral life cycle. Innate immune genes (IIGs) are repressed by HPV16, and we have reported that this repression persists through to cancer. Reversal of this repression would boost the immune response to HPV16 positive tumors, an area that is becoming more important given the advances in immunotherapy. This report demonstrates that E6 and E7 synergistically repress IIG expression in the context of the entire HPV16 genome. Removal of either protein activates the expression of IIGs by HPV16. Therefore, gaining a precise understanding of how the viral oncogenes repress IIG expression represents an opportunity to reverse this repression and boost the immune response to HPV16 infections for therapeutic gain.

1080 Milk yield genotype impacts expression of hepatic innate immune genes during the transition period in Holsteins

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 518-518
Author(s):  
G. T. Cousillas ◽  
W. J. Weber ◽  
B. Walcheck ◽  
D. E. Kerr ◽  
T. H. Elsasser ◽  
...  
Keyword(s):  
Milk Yield ◽  
Transition Period ◽  
Innate Immune ◽  
Immune Genes ◽  
Innate Immune Genes

microRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila

Genetics ◽  
2021 ◽  
Author(s):  
Xiaofen Wu ◽  
Kongyan Niu ◽  
Xiaofan Wang ◽  
Jing Zhao ◽  
Han Wang ◽  
...  
Keyword(s):  
Cell Types ◽  
Innate Immune ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Immune Genes ◽  
Healthy Longevity ◽  
Muscle Tissues ◽  
Distinct Cell ◽  
A Cell ◽  
Innate Immune Genes

Abstract Inflammaging refers to low-grade, chronically activated innate immunity that has deleterious effects on healthy lifespan. However, little is known about the intrinsic signaling pathway that elicits innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-β pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, to repress Daw. Unopposed Daw triggers hyper activation of innate immune genes coupled with a decline in organismal survival. Using adult muscle tissues, single-cell sequencing analysis describes that Daw and its downstream innate immune genes are expressed in distinct cell types, suggesting a cell non-autonomous mode of regulation. We further determine the genetic cascade by which Daw signaling leads to increased Kenny/IKKγ protein, which in turn activates Relish/NF-κB protein and consequentially innate immune genes. Finally, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO promote healthy longevity by cooperative inhibition on Daw mediated inflammaging.

scholarly journals Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans

2017 ◽  
Author(s):  
Song-Hua Lee ◽  
Shizue Omi ◽  
Nishant Thakur ◽  
Clara Taffoni ◽  
Jérôme Belougne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Signaling ◽  
Kinase Inhibitor ◽  
Innate Immune ◽  
Immune Genes ◽  
C Elegans ◽  
Intestinal Infections ◽  
Innate Immune Genes ◽  
Peptide Gene ◽  
Complex Manner

ABSTRACTWhen an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.

CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells

2021 ◽  
Author(s):  
Katja Koeppen ◽  
Amanda B Nymon ◽  
Roxanna Barnaby ◽  
Zhongyou Li ◽  
Thomas H Hampton ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Bacterial Infection ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte derived macrophages (MDM) and contrasts responses of CF and WT MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa, and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC induced immune response genes and increased secretion of pro-inflammatory cytokines, chemoattractants and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.

Sign in / Sign up

Export Citation Format

Share Document