scholarly journals Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster

2021 ◽  
Vol 118 (32) ◽  
pp. e2026554118
Author(s):  
Crystal M. Vincent ◽  
Marc S. Dionne
Keyword(s):  
Drosophila Melanogaster ◽  
Immune Responses ◽  
Negative Regulator ◽  
Sexually Dimorphic ◽  
Wild Type ◽  
Functional Importance ◽  
Immune Activity ◽  
Imd Pathway ◽  
Independent Effects ◽  
Female Specific

Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ for the sexes. Here, by measuring metabolic and physiological outputs in Drosophila melanogaster with wild-type and mutant immune responses, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the immune deficiency (IMD) pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant to infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

scholarly journals Disparate regulation of imd drives sex differences in infection pathology in Drosophila melanogaster

2020 ◽  
Author(s):  
Crystal M. Vincent ◽  
Marc S. Dionne
Keyword(s):  
Drosophila Melanogaster ◽  
Negative Regulator ◽  
Sexually Dimorphic ◽  
Wild Type ◽  
Functional Importance ◽  
Male And Female ◽  
Immune Activity ◽  
Imd Pathway ◽  
Independent Effects ◽  
Female Specific

AbstractMale and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromised Drosophila melanogaster, we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

scholarly journals Analysis of the Doublesex Female Protein in Drosophila melanogaster: Role in Sexual Differentiation and Behavior and Dependence on Intersex

Genetics ◽  
1999 ◽  
Vol 152 (4) ◽  
pp. 1653-1667 ◽  
Author(s):  
Julie A Waterbury ◽  
Larry L Jackson ◽  
Paul Schedl
Keyword(s):  
Drosophila Melanogaster ◽  
Sex Determination ◽  
Target Genes ◽  
Negative Regulator ◽  
Wild Type ◽  
Binding Properties ◽  
Behavioral Abnormalities ◽  
Female Specific ◽  
And Behavior ◽  
Dna Binding Properties

Abstract doublesex (dsx) is unusual among the known sex-determination genes of Drosophila melanogaster in that functional homologs are found in distantly related species. In flies, dsx occupies a position near the bottom of the sex determination hierarchy. It is expressed in male- and female-specific forms and these proteins function as sex-specific transcription factors. In the studies reported here, we have ectopically expressed the female Dsx protein (DsxF) from a constitutive promoter and examined its regulatory activities independent of other upstream factors involved in female sex determination. We show that it functions as a positive regulator of female differentiation and a negative regulator of male differentiation. As predicted by the DNA-binding properties of the Dsx protein, DsxF and DsxM compete with each other for the regulation of target genes. In addition to directing sex-specific differentiation, DsxF plays an important role in sexual behavior. Wild-type males ectopically expressing DsxF are actively courted by other males. This acquisition of feminine sex appeal is likely due to the induction of female pheromones by DsxF. More extreme behavioral abnormalities are observed when DsxF is ectopically expressed in dsx- XY animals; these animals are not only courted by, but also copulate with, wild-type males. Finally, we provide evidence that intersex is required for the feminizing activities of DsxF and that it is not regulated by the sex-specific splicing cascade.

scholarly journals Pleiotropic Roles of the Orthologue of the Drosophila melanogaster Intersex Gene in the Brown Planthopper

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 379
Author(s):  
Hou-Hong Zhang ◽  
Yu-Cheng Xie ◽  
Han-Jing Li ◽  
Ji-Chong Zhuo ◽  
Chuan-Xi Zhang
Keyword(s):  
Drosophila Melanogaster ◽  
Reproductive System ◽  
Splice Variants ◽  
Brown Planthopper ◽  
Nilaparvata Lugens ◽  
Vital Role ◽  
Sexually Dimorphic ◽  
Specific Product ◽  
Reproductive Ability ◽  
Female Specific

Intersex(ix), a gene involved in the sex-determining cascade of Drosophila melanogaster, works in concert with the female-specific product of doublesex (dsx) at the end of the hierarchy to implement the sex-specific differentiation of sexually dimorphic characters in female individuals. In this study, the ix homolog was identified in the brown planthopper (BPH), Nilaparvata lugens, which contained two splice variants expressed in both female and male insects. We found that Nlix played a vital role in the early nymphal development of BPH, showing an accumulated effect. RNAi-mediated knockdown of Nlix at 4th instar led to the external genital defects in both sexes, consequently resulting in the loss of reproductive ability in female and male individuals. After dsRNA injection, the males were normal on testes, while the females had defective ovarian development. Nlix was also required for early embryogenesis. Notably, when the dsNlix microinjection was performed in newly emerged females, the copulatory bursas were abnormally enlarged while the other tissues of the reproductive system developed normally. Our results demonstrated the pleiotropic roles of Nlix in embryogenesis and development of the reproductive system in a hemimetabolous insect species.

scholarly journals Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae

Insects ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 95 ◽  
Author(s):  
Sara Cabral ◽  
Adriano de Paula ◽  
Richard Samuels ◽  
Rodrigo da Fonseca ◽  
Simone Gomes ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Fungal Infection ◽  
Fat Body ◽  
Negative Regulator ◽  
Toll Pathway ◽  
Promising Alternative ◽  
Imd Pathway ◽  
Feeding Regimes

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL−1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.

scholarly journals NITROGEN LIMITATION ADAPTATION functions as a negative regulator of Arabidopsis immunity

2021 ◽  
Author(s):  
Beatriz Val Torregrosa ◽  
Mireia Bundo ◽  
Tzyy Jen Chiou ◽  
Victor Flors ◽  
Blanca San Segundo
Keyword(s):  
Immune Responses ◽  
Transcriptional Activation ◽  
Fungal Pathogens ◽  
Nitrogen Limitation ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Wild Type ◽  
Pathogen Infection ◽  
Fungal Elicitors ◽  
Resistance To Infection

Background: Phosphorus is an important macronutrient required for plant growth and development. It is absorbed through the roots in the form of inorganic phosphate (Pi). To cope with Pi limitation, plants have evolved an array of adaptive mechanisms to facilitate Pi acquisition and protect them from stress caused by Pi starvation. The NITROGEN LIMITATION ADAPTION (NLA) gene plays a key role in the regulation of phosphate starvation responses (PSR), its expression being regulated by the microRNA miR827. Stress caused by Pi limiting conditions might also affect the plant response to pathogen infection. However, cross-talk between phosphate signaling pathways and immune responses remains unclear. Results: In this study, we investigated whether NLA plays a role in Arabidopsis immunity. We show that loss-of-function of NLA and MIR827 overexpression causes an increase in phosphate (Pi) content which results in resistance to infection by the fungal pathogen Plectosphaerella cucumerina. The nla mutant plants accumulated callose in their leaves, a response that is also observed in wild-type plants that have been treated with high Pi. We also show that pathogen infection and treatment with fungal elicitors is accompanied by transcriptional activation of MIR827 and down-regulation of NLA. Upon pathogen challenge, nla plants exhibited higher levels of the phytoalexin camalexin compared to wild type plants. Camalexin level also increases in wild type plants treated with high Pi. Furthermore, the nla mutant plants accumulated salicylic acid (SA) and jasmonic acid (JA) in the absence of pathogen infection whose levels further increased upon pathogen. Conclusions: This study shows that NLA acts as a negative regulator of Arabidopsis immunity. Overaccumulation of Pi in nla plants positively affects resistance to infection by fungal pathogens. This piece of information reinforces the idea of signaling convergence between Pi and immune responses for the regulation of disease resistance in Arabidopsis.

scholarly journals Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2

2003 ◽  
Vol 197 (6) ◽  
pp. 703-709 ◽  
Author(s):  
Nancy Wood ◽  
Matthew J. Whitters ◽  
Bruce A. Jacobson ◽  
JoAnn Witek ◽  
Joseph P. Sypek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immunoglobulin E ◽  
Interferon Γ ◽  
Wild Type ◽  
Functional Importance ◽  
Bone Marrow Macrophage ◽  
Tissue Macrophage ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Deficient Mice

Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)α and IL-13Rα1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Rα2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Rα2, mice deficient in IL-13Rα2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Rα2−/− mice despite the fact that serum IL-13 was absent and immune interferon γ production increased compared with wild-type mice. IL-13Rα2–deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Rα2 in regulating immune responses in wild-type mice.

Mutations at the suppressor of forked locus increase the accumulation of gypsy-encoded transcripts in Drosophila melanogaster

1986 ◽  
Vol 6 (6) ◽  
pp. 2271-2274
Author(s):  
S M Parkhurst ◽  
V G Corces
Keyword(s):  
Drosophila Melanogaster ◽  
Transposable Element ◽  
Negative Regulator ◽  
Developmental Expression ◽  
Wild Type ◽  
Stages Of Development

We studied the effect of mutations at the suppressor of forked [su(f)] locus in Drosophila melanogaster on the accumulation of transcripts encoded by the gypsy transposable element. Mutations at this locus do not affect the pattern of developmental expression of gypsy, but they cause an increase in the total amount of gypsy RNA present at different stages of development as compared with wild-type or su(f)/+ flies. These results suggest that the su(f)-encoded products acts as a negative regulator of gypsy expression.

scholarly journals CD73 Is Critical for the Resolution of Murine Colonic Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Margaret S. Bynoe ◽  
Adam T. Waickman ◽  
Deeqa A. Mahamed ◽  
Cynthia Mueller ◽  
Jeffrey H. Mills ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dextran Sulfate ◽  
Adenosine Monophosphate ◽  
Negative Regulator ◽  
Cellular Damage ◽  
Wild Type ◽  
Extracellular Adenosine ◽  
Glycosyl Phosphatidylinositol ◽  
Cd73 Expression

CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to adenosine. Adenosine is a negative regulator of inflammation and prevents excessive cellular damage. We investigated the role of extracellular adenosine in the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt-induced colitis in mice that lack CD73 (CD73−/−) and are unable to synthesize extracellular adenosine. We have found that, compared to wild-type (WT) mice, CD73−/−mice are highly susceptible to DSS-induced colitis. CD73−/−mice exhibit pronounced weight loss, slower weight recovery, an increase in gut permeability, a decrease in expression of tight junctional adhesion molecules, as well as unresolved inflammation following the removal of DSS. Moreover, colonic epithelia in CD73−/−mice exhibited increased TLR9 expression, high levels of IL-1βand TNF-α, and constitutive activation of NF-κB. We conclude that CD73 expression in the colon is critical for regulating the magnitude and the resolution of colonic immune responses.

scholarly journals Differentiation of a male-specific muscle in Drosophila melanogaster does not require the sex-determining genes doublesex or intersex.

Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 179-191
Author(s):  
B J Taylor
Keyword(s):  
Drosophila Melanogaster ◽  
Abdominal Segment ◽  
Specific Form ◽  
Null Alleles ◽  
Abdominal Muscles ◽  
Sexually Dimorphic ◽  
Wild Type ◽  
Specific Muscle ◽  
Sex Lethal ◽  
Male Specific

Abstract A pair of muscles span the fifth abdominal segment of male but not female Drosophila melanogaster adults. To establish whether genes involved in the development of other sexually dimorphic tissues controlled the differentiation of sex-specific muscles, flies mutant for five known sex-determining genes were examined for the occurrence of male-specific abdominal muscles. Female flies mutant for alleles of Sex-lethal, defective in sex determination, or null alleles of transformer or transformer-2 are converted into phenotypic males that formed male-specific abdominal muscles. Both male and female flies, when mutant for null alleles of doublesex, develop as nearly identical intersexes in other somatic characteristics. Male doublesex flies produced the male-specific muscles, whereas female doublesex flies lacked them. Female flies, even when they inappropriately expressed the male-specific form of doublesex mRNA, failed to produce the male-specific muscles. Therefore, the wild-type products of the genes Sex-lethal, transformer and transformer-2 act to prevent the differentiation of male-specific muscles in female flies. However, there is no role for the genes doublesex or intersex in either the generation of the male-specific muscles in males or their suppression in females.

STUDIES ON THE SEX-SPECIFIC LETHALS OF DROSOPHILA MELANOGASTER. V. SEX TRANSFORMATION CAUSED BY INTERACTIONS BETWEEN A FEMALE-SPECIFIC LETHAL, Sxl  f#1, AND THE MALE-SPECIFIC LETHALS mle(3)132, msl-2  27, AND mle

Genetics ◽  
1982 ◽  
Vol 102 (2) ◽  
pp. 233-243
Author(s):  
T Uenoyama ◽  
A Fukunaga ◽  
K Ioshi
Keyword(s):  
Drosophila Melanogaster ◽  
Morphological Changes ◽  
External Genitalia ◽  
Sexually Dimorphic ◽  
Female Progeny ◽  
Lethal Mutant ◽  
Male Type ◽  
Male Specific Lethal ◽  
Female Specific ◽  
Male Specific

ABSTRACT Interactions between a female-specific lethal mutant, Sxlf  #1, and each of three male-specific lethal mutants, mle(3)132, msl-2  27 and mle, of Drosophila melanogaster were observed to produce morphological changes in various sexually dimorphic external characters. Chromosomal females heterozygous for Sxlf  #1 and homozygous for any one of the male-specific lethals (and to a lesser degree heterozygous for male-specific lethals) sometimes had sex combs, male-type tergites, male-type sternites, male-type anal plates or male-type external genitalia. Penetrance was not high and expression was often incomplete; single individuals never had all the sexually dimorphic structures transformed. When mothers were homozygous for male-specific lethals, higher proportions of female progeny were affected than when mothers were heterozygous, suggesting a maternal effect.

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