scholarly journals Toll and IMD Pathways Synergistically Activate an Innate Immune Response in Drosophila melanogaster

2007 ◽  
Vol 27 (12) ◽  
pp. 4578-4588 ◽  
Author(s):  
Takahiro Tanji ◽  
Xiaodi Hu ◽  
Alexander N. R. Weber ◽  
Y. Tony Ip
Keyword(s):  
Drosophila Melanogaster ◽  
Target Genes ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Peptidoglycan Recognition Protein ◽  
Synergistic Activation ◽  
Independent Functions ◽  
Recognition Protein ◽  
Dual Activation ◽  
Specific Ligand

ABSTRACT The inducible expression of antimicrobial peptide genes in Drosophila melanogaster is regulated by the conserved Toll and peptidoglycan recognition protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways. It has been proposed that the two pathways have independent functions and mediate the specificity of innate immune responses towards different microorganisms. Scattered evidence also suggests that some antimicrobial target genes can be activated by both Toll and IMD, albeit to different extents. This dual activation can be mediated by independent stimulation or by cross-regulation of the two pathways. We show in this report that the Toll and IMD pathways can interact synergistically, demonstrating that cross-regulation occurs. The presence of Spätzle (the Toll ligand) and gram-negative peptidoglycan (the PGRP-LC ligand) together caused synergistic activation of representative target genes of the two pathways, including Drosomycin, Diptericin, and AttacinA. Constitutive activation of Toll and PGRP-LC/IMD could mimic the synergistic stimulation. RNA interference assays and promoter analyses demonstrate that cooperation of different NF-κB-related transcription factors mediates the synergy. These results illustrate how specific ligand binding by separate upstream pattern recognition receptors can be translated into a broad-spectrum host response, a hallmark of innate immunity.

scholarly journals Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e15361 ◽  
Author(s):  
Oana Marcu ◽  
Matthew P. Lera ◽  
Max E. Sanchez ◽  
Edina Levic ◽  
Laura A. Higgins ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses

Comparison of germline mosaics of genes in the Polycomb group of Drosophila melanogaster.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 231-243 ◽  
Author(s):  
M C Soto ◽  
T B Chou ◽  
W Bender
Keyword(s):  
Drosophila Melanogaster ◽  
Target Genes ◽  
Cell Types ◽  
Mitotic Recombination ◽  
Polycomb Group ◽  
Specific Cell ◽  
Independent Functions ◽  
Sex Combs ◽  
Null Phenotype ◽  
Additional Sex Combs

Abstract The genes of the Polycomb group (PcG) repress the genes of the bithorax and Antennapedia complexes, among others. To observe a null phenotype for a PcG gene, one must remove its maternal as well as zygotic contribution to the embryo. Five members of the PcG group are compared here: Enhancer of Polycomb [E(Pc)], Additional sex combs (Asx), Posterior sex combs (Psc), Suppressor of zeste 2 [Su (z) 2] and Polycomblike (Pcl). The yeast recombinase (FLP) system was used to induce mitotic recombination in the maternal germline. Mutant embryos were analyzed by staining with antibodies against six target genes of the PcG. The loss of the maternal component leads to enhanced homeotic phenotypes and to unique patterns of misexpression. E(Pc) and Su(z) 2 mutations had only subtle effects on the target genes, even when the maternal contributions were removed. Asx and Pcl mutants show derepression of the targets only in specific cell types. Psc shows unusual effects on two of the targets, Ultrabithorax and abdominal-A. These results show that the PcG genes do not act only in a common complex or pathway; they must have some independent functions.

scholarly journals Can Salivary Innate Immune Molecules Provide Clue on Taste Dysfunction in COVID-19?

2021 ◽  
Vol 12 ◽  
Author(s):  
Aaron Ermel ◽  
Thankam Paul Thyvalikakath ◽  
Tatiana Foroud ◽  
Babar Khan ◽  
Mythily Srinivasan
Keyword(s):  
Innate Immune ◽  
Host Responses ◽  
Long Term Effects ◽  
Toll Like Receptor 4 ◽  
Angiotensin Converting Enzyme 2 ◽  
Peptidoglycan Recognition Protein ◽  
Recognition Protein ◽  
Taste Dysfunction ◽  
Entry Receptor

Emerging concerns following the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) pandemic are the long-term effects of coronavirus disease (COVID)-19. Dysgeusia in COVID-19 is supported by the abundant expression of the entry receptor, angiotensin-converting enzyme-2 (ACE2), in the oral mucosa. The invading virus perturbs the commensal biofilm and regulates the host responses that permit or suppress viral infection. We correlated the microbial recognition receptors and soluble ACE2 (sACE2) with the SARS-CoV2 measures in the saliva of COVID-19 patients. Data indicate that the toll-like receptor-4, peptidoglycan recognition protein, and sACE2 are elevated in COVID-19 saliva and correlate moderately with the viral load.

scholarly journals A Blueprint for Cancer-Related Inflammation and Host Innate Immunity

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3211
Author(s):  
Lucia García-López ◽  
Isabel Adrados ◽  
Dolors Ferres-Marco ◽  
Maria Dominguez
Keyword(s):  
Drosophila Melanogaster ◽  
Immune Responses ◽  
Gene Networks ◽  
Cost Effective ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Host Interactions ◽  
Powerful Means ◽  
Adult Drosophila

Both in situ and allograft models of cancer in juvenile and adult Drosophila melanogaster fruit flies offer a powerful means for unravelling cancer gene networks and cancer–host interactions. They can also be used as tools for cost-effective drug discovery and repurposing. Moreover, in situ modeling of emerging tumors makes it possible to address cancer initiating events—a black box in cancer research, tackle the innate antitumor immune responses to incipient preneoplastic cells and recurrent growing tumors, and decipher the initiation and evolution of inflammation. These studies in Drosophila melanogaster can serve as a blueprint for studies in more complex organisms and help in the design of mechanism-based therapies for the individualized treatment of cancer diseases in humans. This review focuses on new discoveries in Drosophila related to the diverse innate immune responses to cancer-related inflammation and the systemic effects that are so detrimental to the host.

scholarly journals Meta-analysis of immune induced gene expression changes in diverse Drosophila melanogaster innate immune responses

2021 ◽  
Author(s):  
Ashley L Waring ◽  
Joshua Hill ◽  
Brooke M Allen ◽  
Nicholas M Bretz ◽  
Nguyen Le ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Immune Responses ◽  
Meta Analysis ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Response Factors ◽  
Induced Genes ◽  
Conserved Gene

Background: Organisms are commonly infected by a diverse array of pathogen types including bacteria, fungi, viruses, and parasites, and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression in response to infection. However, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. Results: We performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Conclusions: Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction. These findings provide new insight into transcriptional changes that accompany Drosophila immunity. They may suggest possible roles for the differentially regulated genes in innate immune responses to diverse classes of pathogens, and serve to identify candidate genes for further empirical study of these processes.

scholarly journals Acidosis induces antimicrobial peptide expression and resistance to uropathogenic E. coli infection in kidney collecting duct cells via HIF-1α

2020 ◽  
Vol 318 (2) ◽  
pp. F468-F474 ◽  
Author(s):  
Hu Peng ◽  
Jeffrey M. Purkerson ◽  
Robert S. Freeman ◽  
Andrew L. Schwaderer ◽  
George J. Schwartz
Keyword(s):  
Metabolic Acidosis ◽  
Immune Responses ◽  
Antimicrobial Peptide ◽  
Target Genes ◽  
Collecting Duct ◽  
Innate Immune ◽  
Cell Resistance ◽  
Innate Immune Responses ◽  
E Coli ◽  
Acid Loading

Acute pyelonephritis is frequently associated with metabolic acidosis. We previously reported that metabolic acidosis stimulates expression of hypoxia-inducible factor (HIF)-1α-induced target genes such as stromal derived factor-1 and cathelicidin, an antimicrobial peptide. Since the collecting duct (CD) plays a pivotal role in regulating acid-base homeostasis and is the first nephron segment encountered by an ascending microbial infection, we examined the contribution of HIF-1α to innate immune responses elicited by acid loading of an M-1 immortalized mouse CD cell line. Acid loading of confluent M-1 cells was achieved by culture in pH 6.8 medium supplemented with 5-( N-ethyl- N-isopropyl)-amiloride to block Na+/H+ exchange activity for 24 h. Acid loading induced antimicrobial peptide [cathelicidin and β-defensin (Defb2 and Defb26)] mRNA expression and M-1 cell resistance to uropathogenic Escherichia coli infection to an extent similar to that obtained by inhibition of HIF prolyl hydroxylases, which promote HIF-1α protein degradation. The effect of acid loading on M-1 cell resistance to uropathogenic E. coli infection was reduced by inhibition of HIF-1α (PX-478), and, in combination with prolyl hydroxylase inhibitors, acidosis did not confer additional resistance. Thus, metabolic stress of acidosis triggers HIF-1α-dependent innate immune responses in CD (M-1) cells. Whether pharmacological stabilization of HIF prevents or ameliorates pyelonephritis in vivo warrants further investigation.

scholarly journals α-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Oliver Gordon ◽  
Conor M Henry ◽  
Naren Srinivasan ◽  
Susan Ahrens ◽  
Anna Franz ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Tissue Repair ◽  
Target Genes ◽  
Recombinant Expression ◽  
Innate Immune ◽  
Immune Receptor ◽  
Cytoskeletal Component ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Signalling Cascade

Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised by DNGR-1, an innate immune receptor. Previously we suggested that actin is also a DAMP in Drosophila melanogaster by inducing STAT-dependent genes (<xref ref-type="bibr" rid="bib10">Srinivasan et al., 2016</xref>). Here, we revise that conclusion and report that α-actinin is far more potent than actin at inducing the same STAT response and can be found in trace amounts in actin preparations. Recombinant expression of actin or α-actinin in bacteria demonstrated that only α-actinin could drive the expression of STAT target genes in Drosophila. The response to injected α-actinin required the same signalling cascade that we had identified in our previous work using actin preparations. Taken together, these data indicate that α-actinin rather than actin drives STAT activation when injected into Drosophila.

scholarly journals Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines

2021 ◽  
Vol 12 ◽  
Author(s):  
Ella A. Zuiderwijk-Sick ◽  
Céline van der Putten ◽  
Raissa Timmerman ◽  
Jennifer Veth ◽  
Erica M. Pasini ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Surface Protein ◽  
Innate Immune ◽  
Interleukin 4 ◽  
Transcriptional Level ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Nuclear Extracts

Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Moreover, we show that Toll like receptor (TLR)-induced cytokine production is broadly impaired in IL-4-exposed microglia at the transcriptional level. IL-4 type 2 receptor-mediated signaling is shown to be crucial for the inhibition of microglial innate immune responses. TLR-induced nuclear translocalization of NF-κB appeared intact, and we found no evidence for epigenetic modulation of target genes. By contrast, nuclear extracts from IL-4-exposed microglia contained significantly less NF-κB capable of binding to its DNA consensus site. Further identification of the molecular mechanisms that underlie the inhibition of TLR-induced responses in IL-4-exposed microglia may aid the design of strategies that aim to modulate innate immune responses in the brain, for example in gliomas.

Sign in / Sign up

Export Citation Format

Share Document