Imperial College London

DrMarcDionne

Faculty of Natural SciencesDepartment of Life Sciences

Reader in Innate Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5776m.dionne Website

 
 
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Location

 

G.23Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

47 results found

Tonkin R, Kloeckner A, Najer A, Simoes da Silva C, Echalier C, Dionne M, Edwards A, Stevens Met al., 2022, Bacterial toxin-triggered release of antibiotics from capsosomes protects a fly model from lethal methicillin-resistant Staphylococcus aureus (MRSA) infection, Advanced Healthcare Materials, ISSN: 2192-2640

Journal article

Janssens J, Aibar S, Taskiran II, Ismail JN, Gomez AE, Aughey G, Spanier K, De Rop F, Gonzalez-Blas CB, Dionne M, Grimes K, Quan XJ, Papasokrati D, Hulselmans G, Makhzami S, De Waegeneer M, Christiaens V, Southall T, Aerts Set al., 2022, Decoding gene regulation in the fly brain, NATURE, Vol: 601, Pages: 630-+, ISSN: 0028-0836

Journal article

Marshall EKP, Dionne MS, 2021, Drosophila versus Mycobacteria: A model for mycobacterial host-pathogen interactions, MOLECULAR MICROBIOLOGY, Vol: 117, Pages: 600-609, ISSN: 0950-382X

Journal article

Rose S, Beckwith EJ, Burmester C, May RC, Dionne MS, Rezaval Cet al., 2021, Pre-copulatory reproductive behaviours are preserved in <i>Drosophila melanogaster</i> infected with bacteria

<jats:title>Abstract</jats:title><jats:p>Reproduction and immunity are crucial traits that determine an animal’s fitness. Terminal investment hypothesis predicts that reproductive investment should increase in the face of a mortality risk caused by infection. However, due to competitive allocation of energetic resources, individuals fighting infections are expected to decrease reproductive efforts. While there is evidence for both hypotheses, the factors that determine the choice between these strategies are poorly understood. Here, we assess the impact of bacterial infection on pre-copulatory behaviours in the fruit fly <jats:italic>Drosophila melanogaster</jats:italic>. We found that male flies infected with six different bacteria, including pathogenic and non-pathogenic strains, show no significant differences in courtship intensity and mating success. Similarly, bacterial infections did not affect sexual receptivity in female flies. Our data suggest that pre-copulatory reproductive behaviours remain preserved in infected animals, despite the huge metabolic cost of infection.</jats:p>

Journal article

Vincent CM, Beckwith EJ, Pearson WH, Kierdorf K, Gilestro G, Dionne MSet al., 2021, Infection increases activity via <i>Toll</i> dependent and independent mechanisms in <i>Drosophila melanogaster</i>

<jats:title>Abstract</jats:title><jats:p>Host behavioural changes are among the most apparent effects of infection. ‘Sickness behaviour’ can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here we use a real-time tracking and behavioural profiling platform to show that, in <jats:italic>Drosophila melanogaster</jats:italic>, many systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in several lethal infections. Using various bacteria and <jats:italic>D. melanogaster</jats:italic> immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with <jats:italic>Micrococcus luteus</jats:italic>, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the <jats:italic>Toll</jats:italic> ligand <jats:italic>spätzle</jats:italic> and Toll-pathway activity in the fat body and the brain. In contrast, increased activity after infection with <jats:italic>Francisella novicida</jats:italic>, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of either <jats:italic>spätzle</jats:italic> or the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.</jats:p>

Journal article

Vincent CM, Dionne MS, 2021, Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster, Proceedings of the National Academy of Sciences, Vol: 118, Pages: 1-10, ISSN: 0027-8424

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.

Journal article

Feng Y, Dionne MS, Stamatiades EG, Kierdorf Ket al., 2021, Editorial: deciphering phagocyte functions across different species, Frontiers in Cell and Developmental Biology, Vol: 9, ISSN: 2296-634X

Journal article

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar P, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gomez E, Alessandri C, Ali M, Al-Bari MAA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Alves S, da Costa CA, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Anton Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araujo WL, Araya J, Arden C, Arevalo M-A, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnaune-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Avalos Y, Aveic S, Aveleira CA, AvinWittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae D-H, Bae O-N, Bae SH, Baehrecke EH, Baek A, Baek S-H, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barila D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Jr RCB, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzeet al., 2021, Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy, Vol: 17, Pages: 1-382, ISSN: 1554-8627

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Journal article

Rismondo J, Schulz LM, Yacoub M, Wadhawan A, Hoppert M, Dionne MS, Gründling Aet al., 2021, EslB is required for cell wall biosynthesis and modification in Listeria monocytogenes., Journal of Bacteriology, Vol: 203, Pages: 1-16, ISSN: 0021-9193

Lysozyme is an important component of the innate immune system. It functions by hydrolysing the peptidoglycan (PG) layer of bacteria. The human pathogen Listeria monocytogenes is intrinsically lysozyme resistant. The peptidoglycan N-deacetylase PgdA and O-acetyltransferase OatA are two known factors contributing to its lysozyme resistance. Furthermore, it was shown that the absence of components of an ABC transporter, here referred to as EslABC, leads to reduced lysozyme resistance. How its activity is linked to lysozyme resistance is still unknown. To investigate this further, a strain with a deletion in eslB, coding for a membrane component of the ABC transporter, was constructed in L. monocytogenes strain 10403S. The eslB mutant showed a 40-fold reduction in the minimal inhibitory concentration to lysozyme. Analysis of the PG structure revealed that the eslB mutant produced PG with reduced levels of O-acetylation. Using growth and autolysis assays, we show that the absence of EslB manifests in a growth defect in media containing high concentrations of sugars and increased endogenous cell lysis. A thinner PG layer produced by the eslB mutant under these growth conditions might explain these phenotypes. Furthermore, the eslB mutant had a noticeable cell division defect and formed elongated cells. Microscopy analysis revealed that an early cell division protein still localized in the eslB mutant indicating that a downstream process is perturbed. Based on our results, we hypothesize that EslB affects the biosynthesis and modification of the cell wall in L. monocytogenes and is thus important for the maintenance of cell wall integrity.IMPORTANCE The ABC transporter EslABC is associated with the intrinsic lysozyme resistance of Listeria monocytogenes However, the exact role of the transporter in this process and in the physiology of L. monocytogenes is unknown. Using different assays to characterize an eslB deletion strain, we found that the absence of EslB not only af

Journal article

Vincent CM, Dionne MS, 2020, Disparate regulation of <i>imd</i> drives sex differences in infection pathology in <i>Drosophila melanogaster</i>

<jats:title>Abstract</jats:title><jats:p>Male 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 <jats:italic>Drosophila melanogaster</jats:italic>, 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 <jats:italic>PGRP-LB</jats:italic>, a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of <jats:italic>PGRP-LB</jats:italic>, females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.</jats:p>

Journal article

Vincent C, Simoes da Silva C, Wadhawan A, Dionne Met al., 2020, Origins of metabolic pathology in Francisella-infected Drosophila, Frontiers in Immunology, Vol: 11, ISSN: 1664-3224

The origins and causes of infection pathologies are often not understood. Despite this, the study of infection and immunity relies heavily on the ability to discern between potential sources of pathology. Work in the fruit fly has supported the assumption that mortality resulting from bacterial invasion is largely due to direct host-pathogen interactions, as lower pathogen loads are often associated with reduced pathology, and bacterial load upon death is predictable. However, the mechanisms through which these interactions bring about host death are complex. Here we show that infection with the bacterium Francisella novicida leads to metabolic dysregulation and, using treatment with a bacteriostatic antibiotic, we show that this pathology is the result of direct interaction between host and pathogen. We show that mutants of the immune deficiency immune pathway fail to exhibit similar metabolic dysregulation, supporting the idea that the reallocation of resources for immune-related activities contributes to metabolic dysregulation. Targeted investigation into the cross-talk between immune and metabolic pathways has the potential to illuminate some of this interaction.

Journal article

Rismondo J, Schulz LM, Yacoub M, Wadhawan A, Hoppert M, Dionne MS, Gründling Aet al., 2020, EslB is required for cell wall biosynthesis and modification in<i>Listeria monocytogenes</i>, Publisher: Cold Spring Harbor Laboratory

<jats:title>ABSTRACT</jats:title><jats:p>Lysozyme is an important component of the innate immune system. It functions by hydrolysing the peptidoglycan (PG) layer of bacteria. The human pathogen<jats:italic>Listeria monocytogenes</jats:italic>is intrinsically lysozyme resistant. The peptidoglycan<jats:italic>N</jats:italic>-deacetylase PgdA and<jats:italic>O</jats:italic>-acetyltransferase OatA are two known factors contributing to its lysozyme resistance. Furthermore, it was shown that the absence of components of an ABC transporter, here referred to as EslABC, leads to reduced lysozyme resistance. How its activity is linked to lysozyme resistance is still unknown. To investigate this further, a strain with a deletion in<jats:italic>eslB</jats:italic>, coding for a membrane component of the ABC transporter, was constructed in<jats:italic>L. monocytogenes</jats:italic>strain 10403S. The<jats:italic>eslB</jats:italic>mutant showed a 40-fold reduction in the minimal inhibitory concentration to lysozyme. Analysis of the PG structure revealed that the<jats:italic>eslB</jats:italic>mutant produced PG with reduced levels of<jats:italic>O</jats:italic>-acetylation. Using growth and autolysis assays, we show that the absence of EslB manifests in a growth defect in media containing high concentrations of sugars and increased endogenous cell lysis. A thinner PG layer produced by the<jats:italic>eslB</jats:italic>mutant under these growth conditions might explain these phenotypes. Furthermore, the<jats:italic>eslB</jats:italic>mutant had a noticeable cell division defect and formed elongated cells. Microscopy analysis revealed that an early cell division protein still localized in the<jats:italic>eslB</jats:italic>mutant indicating that a downstream process is perturbed. Based on our results, we hypothesize that EslB affects the b

Working paper

Kierdorf K, Hersperger F, Sharrock J, Vincent C, Ustaoglu P, Dou J, Gyoergy A, Gross O, Siekhaus D, Dionne Met al., 2020, Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila, eLife, Vol: 9, ISSN: 2050-084X

Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis.

Journal article

Kierdorf K, Hersperger F, Sharrock J, Vincent CM, Ustaoglu P, Dou J, Gyoergy A, Groß O, Siekhaus DE, Dionne MSet al., 2019, Muscle function and homeostasis require macrophage-derived cytokine inhibition of AKT activity in <i>Drosophila</i>, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p><jats:italic>Unpaired</jats:italic> ligands are secreted signals that act via a GP130-like receptor, <jats:italic>domeless</jats:italic>, to activate JAK-STAT signaling in <jats:italic>Drosophila</jats:italic>. Like many mammalian cytokines, <jats:italic>unpaireds</jats:italic> can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for <jats:italic>unpaired</jats:italic>-JAK signaling as a metabolic regulator in healthy adult <jats:italic>Drosophila</jats:italic> muscle. Adult muscles show basal JAK-STAT signaling activity in the absence of any immune challenge. Macrophages are the source of much of this tonic signal. Loss of the <jats:italic>dome</jats:italic> receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal from macrophages to muscle that controls AKT activity and metabolic homeostasis.</jats:p>

Working paper

Sharrock J, Estacio Gomez A, Jacobson J, Kierdorf K, Southall T, Dionne Met al., 2019, fs(1)h controls metabolic and immune function and enhances survival via AKT and FOXO in Drosophila, Disease Models & Mechanisms, Vol: 12, ISSN: 1754-8403

The Drosophila fat body is the primary organ of energy storage as well as being responsible for the humoral response to infection. Its physiological function is of critical importance to the survival of the organism; however, many molecular regulators of its function remain ill-defined. Here, we show that the Drosophila melanogaster bromodomain-containing protein FS(1)H is required in the fat body for normal lifespan as well as metabolic and immune homeostasis. Flies lacking fat body fs(1)h exhibit short lifespan, increased expression of immune target genes, an inability to metabolize triglyceride, and low basal AKT activity, mostly resulting from systemic defects in insulin signalling. Removal of a single copy of the AKT-responsive transcription factor foxo normalises lifespan, metabolic function, uninduced immune gene expression and AKT activity. We suggest that the promotion of systemic insulin signalling activity is a key in vivo function of fat body fs(1)h.

Journal article

Gordon O, Henry CM, Srinivasan N, Ahrens S, Franz A, Deddouche S, Chakravarty P, Phillips D, George R, Kjaer S, Frith D, Snijders AP, Valente RS, da Silva CJS, Teixeira L, Thompson B, Dionne MS, Wood W, Reis e Sousa Cet al., 2018, alpha-actinin accounts for the bioactivity of actin preparations in inducing STAT target genes in Drosophila melanogaster, eLife, Vol: 7, ISSN: 2050-084X

Damage-associated molecular patterns (DAMPs) are molecules exposed or released bydead cells that trigger or modulate immunity and tissue repair. In vertebrates, the cytoskeletalcomponent 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 STATdependent genes (Srinivasan et al., 2016). Here, we revise that conclusion and report that aactinin is far more potent than actin at inducing the same STAT response and can be found in traceamounts in actin preparations. Recombinant expression of actin or a-actinin in bacteriademonstrated that only a-actinin could drive the expression of STAT target genes in Drosophila.The response to injected a-actinin required the same signalling cascade that we had identified inour previous work using actin preparations. Taken together, these data indicate that a-actininrather than actin drives STAT activation when injected into Drosophila.

Journal article

Pean CB, Schiebler M, Tan S, Sharrock J, Kierdorf K, Brown K, Maserumule M, Menezes S, Platova M, Bronda K, Guermonprez P, Stramer BM, Floto R, Dionne MS, Pean CB, Schiebler M, Tan SWS, Sharrock JA, Kierdorf K, Brown KP, Maserumule MC, Menezes S, Pilatova M, Bronda K, Guermonprez P, Stramer BM, Floto RA, Dionne MSet al., 2017, Regulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection, Nature Communications, Vol: 8, Pages: 1-11, ISSN: 2041-1723

Mycobacterium tuberculosis remains a global threat to human health yet the molecular mechanisms regulating immunity remain poorly understood. Cytokines can promote or inhibit mycobacterial survivalinside macrophages, andthe underlying mechanisms represent potential targets for host-directed therapies. Here we show that cytokine-STAT signaling promotesmycobacterial survivalwithin macrophages by deregulating lipid droplets via ATG2 repression. In Drosophilainfected withMycobacterium marinum,mycobacterium-induced STAT activitytriggered by unpaired-familycytokinesreduces Atg2 expression, permittingderegulation of lipid droplets. Increased Atg2expression, or reduced macrophage triglyceride biosynthesis,normalizes lipid deposition in infected phagocytes and reduces numbersof viable intracellular mycobacteria. In human macrophages,addition ofIL-6promotes mycobacterial survival and BCG-induced lipid accumulation by a similar, but probably not identical, mechanism. Our results reveal Atg2regulation as amechanism by which cytokines can control lipid droplet homeostasis and consequently resistance to mycobacterial infectionin Drosophila.

Journal article

Srinivasan N, Gordon O, Ahrens S, Franz A, Deddouche S, Chakravarty P, Phillips D, Yunus AA, Rosen MK, Valente RS, Teixeira L, Thompson B, Dionne MS, Wood W, Reis e Sousa Cet al., 2016, Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster, eLife, Vol: 5, ISSN: 2050-084X

Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity.

Journal article

Kierdorf K, Dionne MS, 2016, The software and hardware of macrophages: a diversity of options, Developmental Cell, Vol: 38, Pages: 122-125, ISSN: 1878-1551

Macrophages play important immune and homeostatic roles that depend on the ability to receive and interpret specific signals from environmental stimuli. Here we describe the different activation states these cells can exhibit in response to signals and how these states affect and can be affected by bacterial pathogens.

Journal article

Cagin U, Duncan OF, Gatt AP, Dionne MS, Sweeney ST, Bateman JMet al., 2015, Erratum: Mitochondrial retrograde signaling regulates neuronal function (Proceedings of the National Academy of Sciences of the United States of America (2015) 112 (E6000-E6009) DOI 10.1073/pnas.1505036112), Proceedings of the National Academy of Sciences of the United States of America, Vol: 112, ISSN: 0027-8424

Journal article

Cagin U, Duncan OF, Gatt AP, Dionne MS, Sweeney ST, Bateman JMet al., 2015, Mitochondrial retrograde signaling regulates neuronal function, Proceedings of the National Academy of Sciences of the United States of America, Vol: 112, Pages: E6000-E6009, ISSN: 0027-8424

Mitochondria are key regulators of cellular homeostasis, and mitochondrial dysfunction is strongly linked to neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Mitochondria communicate their bioenergetic status to the cell via mitochondrial retrograde signaling. To investigate the role of mitochondrial retrograde signaling in neurons, we induced mitochondrial dysfunction in the Drosophila nervous system. Neuronal mitochondrial dysfunction causes reduced viability, defects in neuronal function, decreased redox potential, and reduced numbers of presynaptic mitochondria and active zones. We find that neuronal mitochondrial dysfunction stimulates a retrograde signaling response that controls the expression of several hundred nuclear genes. We show that the Drosophila hypoxia inducible factor alpha (HIFα) ortholog Similar (Sima) regulates the expression of several of these retrograde genes, suggesting that Sima mediates mitochondrial retrograde signaling. Remarkably, knockdown of Sima restores neuronal function without affecting the primary mitochondrial defect, demonstrating that mitochondrial retrograde signaling is partly responsible for neuronal dysfunction. Sima knockdown also restores function in a Drosophila model of the mitochondrial disease Leigh syndrome and in a Drosophila model of familial Parkinson’s disease. Thus, mitochondrial retrograde signaling regulates neuronal activity and can be manipulated to enhance neuronal function, despite mitochondrial impairment.

Journal article

Woodcock KJ, Kierdorf K, Pouchelon CA, Vivancos V, Dionne MS, Geissmann Fet al., 2015, Macrophage-derived upd3 Cytokine causes impaired glucose homeostasis and reduced lifespan in drosophila fed a lipid-rich diet, Immunity, Vol: 42, Pages: 133-144, ISSN: 1097-4180

Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic activation of JAK-STAT signaling, reduced insulin sensitivity, hyperglycemia, and a shorter lifespan. Drosophila macrophages produced the JAK-STAT-activating cytokine upd3, in a scavenger-receptor (crq) and JNK-dependent manner. Genetic depletion of macrophages or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-κB signaling made no contribution to the phenotype observed. These results identify an evolutionarily conserved “scavenger receptor-JNK-type 1 cytokine” cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway.

Journal article

Colas C, Menezes S, Gutierrez-Martinez E, Pean CB, Dionne MS, Guermonprez Pet al., 2014, An improved flow cytometry assay to monitor phagosome acidification, JOURNAL OF IMMUNOLOGICAL METHODS, Vol: 412, Pages: 1-13, ISSN: 0022-1759

Journal article

Stramer BM, Dionne MS, 2014, Unraveling tissue repair immune responses in flies, SEMINARS IN IMMUNOLOGY, Vol: 26, Pages: 310-314, ISSN: 1044-5323

Journal article

Dionne MS, 2014, Immune-metabolic interaction in Drosophila, FLY, Vol: 8, Pages: 75-79, ISSN: 1933-6934

Journal article

Pean CB, Dionne MS, 2014, Intracellular infections in Drosophila melanogaster: Host defense and mechanisms of pathogenesis, DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, Vol: 42, Pages: 57-66, ISSN: 0145-305X

Journal article

Clark RI, Walker DW, Dionne MS, 2014, Metabolic and immune integration in aging and age-related disease, AGING-US, Vol: 6, Pages: 3-4, ISSN: 1945-4589

Journal article

Clark RI, Tan SWS, Pean CB, Roostalu U, Vivancos V, Bronda K, Pilatova M, Fu J, Walker DW, Berdeaux R, Geissmann F, Dionne MSet al., 2013, MEF2 Is an In Vivo Immune-Metabolic Switch, CELL, Vol: 155, Pages: 435-447, ISSN: 0092-8674

Journal article

Dionne MS, 2013, Comparative immunology: allorecognition and variable surface receptors outside the jawed vertebrates, CURRENT OPINION IN IMMUNOLOGY, Vol: 25, Pages: 608-612, ISSN: 0952-7915

Journal article

Pilatova M, Dionne MS, 2012, Burkholderia thailandensis Is Virulent in Drosophila melanogaster, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

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