Article
Biochemistry & Molecular Biology
Wanwan Pan, Xiaolong Yao, Lu Lin, Xiaoqi Liu, Ping Jin, Fei Ma
Summary: This study reveals a novel mechanism by which Relish regulates Drosophila immune homeostasis through a negative feedback loop, where Relish activates the transcription of miR-275, which then inhibits the expression of Dredd, resulting in negative control of immune response.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Yangyang Zhu, Qingshuang Cai, Xianrui Zheng, Lei Liu, Yongzhi Hua, Beibei Du, Guomin Zhao, Jiangliu Yu, Zhao Zhuo, Zhongwen Xie, Shanming Ji
Summary: The study showed that long-term intake of aspirin can significantly prevent age-related gut leakage, intestinal stem cell over-proliferation, and dysbiosis in fruit flies. Aspirin downregulates chronic activation of intestinal immune deficiency signaling during aging, positively modulating intestinal homeostasis and delaying aging in Drosophila.
Article
Multidisciplinary Sciences
Crystal M. Vincent, Marc S. Dionne
Summary: Male and female animals show differences in infection outcomes, with potential sources of sexually dimorphic immunity being the sex-specific costs of immune activity or pathology. This study found that males and females exhibit differential immune activity but similar bacteria-derived metabolic pathology, with females having a female-specific immune-inducible expression of PGRP-LB which plays a critical role in reducing immune activity in response to bacterial reductions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Shirong Li, Jing Wang, Xing Tian, Shahzad Toufeeq, Wuren Huang
Summary: This paper reviews the research progress of insect immune-metabolism regulation, emphasizing the importance of metabolic transformations during immune cell activation and the impact of symbiotic bacteria on insect physiology. It provides guidance for uncovering immune-metabolism mechanisms and formulating pest control strategies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chihyun Won, Kyungju Nam, Donghee Ko, Byungjun Kang, Im-Soon Lee
Summary: The inactivation of nuclear receptor-binding SET domain-containing protein 1 (NSD1) in tumor cells contributes to an immune-cold phenotype, suggesting its involvement in immune disruptions. The study investigates the effect of NSD overexpression in the fat body of Drosophila and finds that it increases the mRNA levels of antimicrobial peptides, mainly through the IMD pathway by activating Relish. Further analysis shows that NSD overexpression has a positive role in the immune defenses of Drosophila. These findings provide insights into the molecular mechanisms of immune dysfunction in NSD1-associated human diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Qingyang Li, Chao Zhang, Chuchu Zhang, Renjie Duan, Yongzhi Hua
Summary: In this study, the immune function of CG4968, which encodes a typical OTU-type Dub in Drosophila melanogaster, was explored. The results showed that CG4968 plays a positive regulatory role in the IMD pathway, but not the Toll pathway, in a manner dependent on the OTU domain. Mechanistically, CG4968 was found to be associated with Imd and restrict its K48-linked ubiquitination, thereby contributing to its turnover. This study uncovered a novel regulatory mechanism involving the K48-linked ubiquitination of Imd in Drosophila innate immunity.
Article
Cardiac & Cardiovascular Systems
Hideaki Inazumi, Koichiro Kuwahara, Yasuaki Nakagawa, Yoshihiro Kuwabara, Takuro Numaga-Tomita, Toshihide Kashihara, Tsutomu Nakada, Nagomi Kurebayashi, Miku Oya, Miki Nonaka, Masami Sugihara, Hideyuki Kinoshita, Kenji Moriuchi, Hiromu Yanagisawa, Toshio Nishikimi, Hirohiko Motoki, Mitsuhiko Yamada, Sachio Morimoto, Kinya Otsu, Richard M. Mortensen, Kazuwa Nakao, Takeshi Kimura
Summary: NRSF is a transcriptional repressor that suppresses the reactivation of fetal cardiac gene program and maintains cardiac integrity. This study reveals that NRSF regulates ventricular function by controlling the expression of G alpha(o) gene, and excessive expression of G alpha(o) leads to cardiac dysfunction. Additionally, G alpha(o) plays a critical role in cardiac Ca2+ homeostasis and systolic function.
CIRCULATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Qingshuang Cai, Shanming Ji, Mengwan Li, Sen Zheng, Xiuhong Zhou, Huimin Guo, Siyu Deng, Junyan Zhu, Daxiang Li, Zhongwen Xie
Summary: Theaflavins have been shown to delay aging in Drosophila by preventing age-onset intestinal leakage and dysbiosis, while also playing a role in modulating intestinal integrity in mice through regulating Imd signals.
Article
Cell Biology
Ping Zhang, Zhichao Yao, Shuai Bai, Hongyu Zhang
Summary: In this study, three catalytic PGRPs family genes, BdPGRP-LB, BdPGRP-SB1, and BdPGRP-SC2, were identified and functionally characterized in B. dorsalis. The results revealed that these genes play important roles as negative regulators of the Imd pathway in the insect's immune response. Silencing of these genes resulted in over-activation of the Imd signaling pathway after bacterial challenge.
Article
Multidisciplinary Sciences
Pragya Prakash, Arghyashree Roychowdhury-Sinha, Akira Goto
Summary: A new negative regulator of the IMD pathway in Drosophila, Velo, has been identified, with its knock-down leading to constitutive expression of AMPs and enhanced antimicrobial peptide expression upon bacterial stimulation. Velo is found to reside in both the nucleus and cytoplasm, and its downregulation results in increased immune response and reduced bacterial load, making the flies more susceptible to infection.
SCIENTIFIC REPORTS
(2021)
Article
Physiology
Hye Jin Ko, Bharat Bhusan Patnaik, Ki Beom Park, Chang Eun Kim, Snigdha Baliarsingh, Ho Am Jang, Yong Seok Lee, Yeon Soo Han, Yong Hun Jo
Summary: In this study, a homolog of IKK epsilon (TmIKK epsilon) was identified and characterized for its role in regulating immune signaling pathways in insects. The expression of TmIKK epsilon was induced by microbial challenge and its knockdown reduced the survival of insects against microbial infections.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Oncology
Min Liu, Runmei Li, Min Wang, Ting Liu, Qiuru Zhou, Dong Zhang, Jian Wang, Meng Shen, Xiubao Ren, Qian Sun
Summary: This study found that PGAM1 is upregulated and associated with poor prognosis in breast cancer patients. Functional experiments showed that knockdown of PGAM1 suppresses the biological behavior of breast cancer cells. RNA sequencing revealed that ASS1 expression is significantly upregulated following PGAM1 knockdown and is essential for suppressing the malignant behavior of breast cancer cells. Importantly, the study demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments validated that PGAM1 promotes tumor growth in breast cancer by altering ASS1 expression. Immunohistochemical analysis showed that downregulated ASS1 levels are associated with PGAM1 expression and poor prognosis in breast cancer patients.
MOLECULAR ONCOLOGY
(2022)
Article
Biology
David Romano, Lucia Garcia-Gutierrez, Nourhan Aboud, David J. Duffy, Keith T. Flaherty, Dennie T. Frederick, Walter Kolch, David Matallanas
Summary: This study reveals that the MST2 pathway plays a critical role in the development of resistance to BRAF inhibitors in malignant melanoma. The BRAFV600E mutant protein inhibits the proapoptotic signaling of the MST2 pathway by binding to MST2, reducing apoptosis induced by BRAF inhibitors. In BRAF inhibitor-resistant cell lines, MST2 pathway proteins are down-regulated through ubiquitination and subsequent proteasomal degradation, rendering cells resistant to MST2 pathway-induced apoptosis.
LIFE SCIENCE ALLIANCE
(2022)
Article
Plant Sciences
Maite Colinas, Jacob Pollier, Dries Vaneechoutte, Deniz G. Malat, Fabian Schweizer, Liesbeth De Milde, Rebecca De Clercq, Joana G. Guedes, Teresa Martinez-Cortes, Francisco J. Molina-Hidalgo, Mariana Sottomayor, Klaas Vandepoele, Alain Goossens
Summary: Catharanthus roseus produces a variety of MIA metabolites in a heavily branched pathway, with gene expression being highly specific to cell type, organ, and stress. Further study of ORCA TFs reveals subfunctionalization in terms of regulating target genes and working synergistically with MYC2. Specific amino acid residues within ORCA DNA-binding domains play a role in regulating MIA pathway branches differently.
FRONTIERS IN PLANT SCIENCE
(2021)
Editorial Material
Cell Biology
Panagiotis Tsapras, Ioannis P. Nezis
Summary: Macroautophagy/autophagy-related protein Atg8/LC3 plays a crucial role in autophagosome formation and selective degradation of various substrates. A recent study identified several proteins that interact with Atg8a, the Drosophila homolog of Atg8/LC3. Among these proteins, Tak1 and its co-activator Tab2 were found to interact with Atg8a and be subjected to selective autophagic clearance. Additionally, SH3PX1 was shown to interact with Tab2 and play a role in regulating the immune-deficiency (IMD) pathway. These findings provide insights into the regulatory interactions between Tak1-Tab2-SH3PX1 and Atg8a, contributing to the fine-tuning of the IMD pathway.
Article
Multidisciplinary Sciences
Elodie Ramond, Jan Paul Dudzic, Bruno Lemaitre
Article
Biochemistry & Molecular Biology
Sandy Al Hayek, Ahmad Alsawadi, Zakaria Kambris, Jean-Philippe Boquete, Jerome Bohere, Clement Immarigeon, Brice Ronsin, Serge Plaza, Bruno Lemaitre, Francois Payre, Dani Osman
Summary: The research uncovers a cell-intrinsic role of the OvoL family transcription factor Shavenbaby (Svb) in balancing self-renewal and differentiation of Drosophila intestinal stem cells, mediated by the downstream target of Wnt and EGFR pathways. The switch between Svb repressor and activator is triggered by systemic steroid hormone, adjusting stem cell proliferation versus differentiation and suggesting a broad role of OvoL/Svb in adult and cancer stem cells.
Editorial Material
Cell Biology
Claudine Neyen
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Genetics & Heredity
Michael Gerth, Humberto Martinez-Montoya, Paulino Ramirez, Florent Masson, Joanne S. Griffin, Rodolfo Aramayo, Stefanos Siozios, Bruno Lemaitre, Mariana Mateos, Gregory D. D. Hurst
Summary: Studies have shown that Spiroplasma has a rapid evolutionary rate, high substitution rate, significant genomic structural differences, and the absence of mismatch repair loci may contribute to the elevated substitution rates. Different Spiroplasma lineages exhibit dynamic evolution in their morphology, and loci similar to the malekilling toxin Spaid have been identified in various Spiroplasma strains and other endosymbionts.
MICROBIAL GENOMICS
(2021)
Article
Multidisciplinary Sciences
Florent Masson, Samuel Rommelaere, Alice Marra, Fanny Schuepfer, Bruno Lemaitre
Summary: Insects are frequently infected with heritable bacterial endosymbionts, which have a significant impact on host physiology and evolution. This study reveals the chronic activation of the Toll immune pathway by the endosymbiont Spiroplasma poulsonii in Drosophila hemolymph through dual proteomics analysis, which was not detected by transcriptomics-based approaches. Candidate proteins potentially involved in controlling S. poulsonii growth were also identified through Drosophila genetics.
Article
Biochemistry & Molecular Biology
Bianca Petrignani, Samuel Rommelaere, Ketty Hakim-Mishnaevski, Florent Masson, Elodie Ramond, Reut Hilu-Dadia, Mickael Poidevin, Shu Kondo, Estee Kurant, Bruno Lemaitre
Summary: This study reveals the crucial role of the Nimrod family member NimB4 in the clearance of apoptotic cells in Drosophila, particularly in phagosome maturation, possibly through binding to apoptotic corpses to engage a phagosome maturation program dedicated to efferocytosis.
Article
Microbiology
A. Marra, M. A. Hanson, S. Kondo, B. Erkosar, B. Lemaitre
Summary: This study demonstrates that the immune effectors, antimicrobial peptides, and lysozymes actively regulate the composition and abundance of gut microbiota in fruit flies. Loss of these immune effectors exacerbates during aging, leading to increased microbiota abundance and shifted composition in aged flies. The findings suggest that immune effectors, known for resistance against pathogens, also influence the beneficial gut community composition.
Article
Microbiology
Mark Austin Hanson, Lianne B. Cohen, Alice Marra, Igor Iatsenko, Steven A. Wasserman, Bruno Lemaitre
Summary: The fruit fly Drosophila melanogaster produces a variety of effector peptides to combat microbial infection, including a novel antifungal peptide gene named Baramicin A. This gene is strongly induced in the fat body downstream of the Toll pathway and plays a key role in the antimicrobial response of the fruit fly.
Article
Genetics & Heredity
Alexia L. Carboni, Mark A. Hanson, Scott A. Lindsay, Steven A. Wasserman, Bruno Lemaitre
Summary: Cecropins are small helical secreted peptides with antimicrobial activity that play an important role in host defense. Experimental studies have shown that Cecropins play a role in defense against Gram-negative bacteria and fungi in fruit flies.
Article
Multidisciplinary Sciences
Florent Masson, Xavier Pierrat, Bruno Lemaitre, Alexandre Persat
Summary: A rigid cell wall defines bacteria morphology, but wall-less Spiroplasma have five homologs of MreB. Research shows that these homologs play a key role in forming a polymeric cytoskeleton in shaping the cell.
Article
Multidisciplinary Sciences
Florent Masson, Samuel Rommelaere, Fanny Schupfer, Jean-Philippe Boquete, Bruno Lemaitre
Summary: The abundance and amino acid composition of a protein called Spiralin B (SpiB) plays a crucial role in the nutritional interactions between insects and their endosymbionts. Increasing SpiB levels disrupts the localization of endosymbionts in insect eggs and decreases vertical transmission. This protein ensures the durability of the interaction in a variable environment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
M. A. Hanson, S. Kondo, B. Lemaitre
Summary: Antimicrobial peptides (AMPs) play a crucial role in defending against infection in plants and animals. A study on Drosophila has revealed that the Drosocin gene encodes two prominent host defense peptides with different specificities against distinct pathogens.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Mark Hanson, Bruno Lemaitre
Summary: Antimicrobial peptides (AMPs) are host-encoded antibiotics that not only combat invading pathogens, but also have roles in neurological contexts. The evolutionary history of Baramicin genes reveals how they have adapted for either immune-specific or neurological roles, providing a case study for how AMP-encoding genes might play dual roles in both immune and non-immune processes via their multiple peptide products.
Article
Cell Biology
Mark A. Hanson, Bruno Lemaitre
Summary: Antimicrobial peptides (AMPs) play important roles in host defense and have been implicated in the clearance of aberrant cells and neurodegenerative syndromes. AMPs are produced in Drosophila downstream of Toll and Imd NF-κB pathways and have antimicrobial properties. Aging leads to upregulation of AMPs, potentially contributing to age-associated inflammatory diseases. However, the individual effects of AMPs on lifespan have been inconclusive. In this study, the researchers found no significant effect of individual AMPs on lifespan, except for Defensin. However, flies lacking seven AMP gene families displayed a reduced lifespan due to microbiome dysbiosis, and germ-free conditions extended their lifespan. Overall, AMPs collectively impact lifespan by preventing dysbiosis during aging.
DISEASE MODELS & MECHANISMS
(2023)
Article
Multidisciplinary Sciences
M. A. Hanson, L. Grollmus, B. Lemaitre
Summary: Antimicrobial peptides, encoded by the host, play a crucial role in combating pathogens and shaping the microbiome in plants and animals. This study focuses on the Diptericin antimicrobial peptide family of Diptera and reveals the specific roles of DptA and DptB in Drosophila melanogaster, demonstrating how they interact with different bacteria. The findings also highlight the correlation between the presence of DptA- or DptB-like genes and the presence of specific bacteria across Diptera.