82 results found
Duggan GM, Mostowy S, 2018, Use of zebrafish to study Shigella infection, DISEASE MODELS & MECHANISMS, Vol: 11, ISSN: 1754-8403
Inglesfield S, Jasiulewicz A, Hopwood M, et al., 2018, Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor circinelloides in Innate Granulomas In Vivo., MBio, Vol: 9
Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by Mucor circinelloides spores are modeled by a combined in silico modeling approach and real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset in vivoIn silico analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These in silico data are supported by an in vivo lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas in vivo Disease can be reactivated by immunosuppression. Together, these data represent the first in vivo real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.IMPORTANCE Mucormycosis is a dramatic fungal infection frequently leading to the death of patients. We know little about the immune response to the fungus causing this infection, although evidence points toward defects in early immune events after infection. Here, we dissect this early immune response to infectious fungal spores.
Sancho-Shimizu V, Mostowy S, 2018, Bacterial Autophagy: How to Take a Complement, Cell Host and Microbe, ISSN: 1931-3128
© 2018 Elsevier Inc. Complement, a complex system of serum proteins, contributes to host defense through multiple mechanisms. In this issue of Cell Host & Microbe, Sorbara et al. (2018) discovered that cytosolic pathogens opsonized by complement are restricted by autophagy. This unexpected role for complement is important for cell-autonomous immunity in the intestinal mucosa. Complement, a complex system of serum proteins, contributes to host defense through multiple mechanisms. In this issue of Cell Host & Microbe, Sorbara et al. (2018) discovered that cytosolic pathogens opsonized by complement are restricted by autophagy. This unexpected role for complement is important for cell-autonomous immunity in the intestinal mucosa.
Torraca V, Mostowy S, 2018, Zebrafish Infection: From Pathogenesis to Cell Biology, TRENDS IN CELL BIOLOGY, Vol: 28, Pages: 143-156, ISSN: 0962-8924
Lee PP, Lobato-Marquez D, Pramanik N, et al., 2017, Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723
Liew N, Moya MJM, Wierzbicki CJ, et al., 2017, Chytrid fungus infection in zebrafish demonstrates that the pathogen can parasitize non-amphibian vertebrate hosts, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723
Lobato-Marquez D, Mostowy S, 2017, Salmonella ubiquitination: ARIH1 enters the fray, EMBO REPORTS, Vol: 18, Pages: 1476-1477, ISSN: 1469-221X
Mazon-Moya MJ, Willis AR, Torraca V, et al., 2017, Septins restrict inflammation and protect zebrafish larvae from Shigella infection, PLOS PATHOGENS, Vol: 13, ISSN: 1553-7366
McCarthy RR, Mazon-Moya MJ, Moscoso JA, et al., 2017, Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to Pseudomonas aeruginosa immune evasion, NATURE MICROBIOLOGY, Vol: 2, ISSN: 2058-5276
Mesquita FS, Brito C, Mazon Moya MJ, et al., 2017, Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins, EMBO REPORTS, Vol: 18, Pages: 303-318, ISSN: 1469-221X
Ribet D, Boscaini S, Cauvin C, et al., 2017, SUMOylation of human septins is critical for septin filament bundling and cytokinesis, JOURNAL OF CELL BIOLOGY, Vol: 216, Pages: 4041-4052, ISSN: 0021-9525
Yoshida N, Frickel E-M, Mostowy S, 2017, Macrophage-Microbe interactions: Lessons from the Zebrafish Model, FRONTIERS IN IMMUNOLOGY, Vol: 8, ISSN: 1664-3224
Klionsky DJ, Abdelmohsen K, Abe A, et al., 2016, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), AUTOPHAGY, Vol: 12, Pages: 1-222, ISSN: 1554-8627
Klionsky DJ, Abdelmohsen K, Abe A, et al., 2016, Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356, Autophagy, Vol: 12, ISSN: 1554-8627
Krokowski S, Lobato-Márquez D, Mostowy S, 2016, Mitochondria promote septin assembly into cages that entrap Shigella for autophagy., Autophagy, Pages: 1-2
Septins are cytoskeletal proteins implicated in cytokinesis and host-pathogen interactions. During macroautophagy/autophagy of Shigella flexneri, septins assemble into cage-like structures to entrap actin-polymerizing bacteria and restrict their dissemination. How septins assemble to entrap bacteria is not fully known. We discovered that mitochondria support septin cage assembly to promote autophagy of Shigella. Consistent with roles for the cytoskeleton in mitochondrial dynamics, we showed that DNM1L/DRP1 (dynamin 1 like) can interact with septins to enhance mitochondrial fission. Remarkably, Shigella fragment mitochondria and escape from septin cage entrapment in order to avoid autophagy. These results uncover a close relationship between mitochondria and septin assembly, and identify a new role for mitochondria in bacterial autophagy.
Krokowski S, Mostowy S, 2016, Interactions between Shigella flexneri and the Autophagy Machinery, FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol: 6, ISSN: 2235-2988
Krokowski S, Mostowy S, 2016, Investigation of septins using infection by bacterial pathogens, SEPTINS, Vol: 136, Pages: 117-134, ISSN: 0091-679X
Larrouy-Maumus G, Clements A, Filloux A, et al., 2016, Direct detection of lipid A on intact Gram-negative bacteria by MALDI-TOF mass spectrometry, JOURNAL OF MICROBIOLOGICAL METHODS, Vol: 120, Pages: 68-71, ISSN: 0167-7012
Lobato-Marquez D, Mostowy S, 2016, Septins recognize micron-scale membrane curvature, JOURNAL OF CELL BIOLOGY, Vol: 213, Pages: 5-6, ISSN: 0021-9525
Pfanzelter J, Way M, Mostowy S, 2016, Septins suppress the release of vaccinia virus from infected cells., Annual Meeting of the American-Society-for-Cell-Biology (ASCB), Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Shah A, Kannambath S, Herbst S, et al., 2016, Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 194, Pages: 1127-1139, ISSN: 1073-449X
Sirianni A, Krokowski S, Lobato-Marquez D, et al., 2016, Mitochondria mediate septin cage assembly to promote autophagy of Shigella, EMBO REPORTS, Vol: 17, Pages: 1029-1043, ISSN: 1469-221X
Torraca V, Mostowy S, 2016, Septins and Bacterial Infection., Front Cell Dev Biol, Vol: 4, ISSN: 2296-634X
Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics.
Willis A, Mazon-Moya M, Mostowy S, 2016, Investigation of septin biology in vivo using zebrafish, SEPTINS, Vol: 136, Pages: 221-241, ISSN: 0091-679X
Willis AR, Moore C, Mazon-Moya M, et al., 2016, Injections of Predatory Bacteria Work Alongside Host Immune Cells to Treat Shigella Infection in Zebrafish Larvae, CURRENT BIOLOGY, Vol: 26, Pages: 3343-3351, ISSN: 0960-9822
Gibbings D, Mostowy S, Jay F, et al., 2015, Selective autophagy degrades DICER and AGO2 and regulates miRNA activity (vol 14, pg 1314, 2012), NATURE CELL BIOLOGY, Vol: 17, Pages: 1088-1088, ISSN: 1465-7392
Herbst S, Shah A, Moya MM, et al., 2015, Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus, EMBO MOLECULAR MEDICINE, Vol: 7, Pages: 240-258, ISSN: 1757-4676
Mostowy S, Shenoy AR, 2015, The cytoskeleton in cell-autonomous immunity: structural determinants of host defence, NATURE REVIEWS IMMUNOLOGY, Vol: 15, Pages: 559-573, ISSN: 1474-1733
Shah A, Kannambath S, Herbst S, et al., 2015, 'THE KISS OF DEATH' - CALCINEURIN INHIBITORS PREVENT ACTIN-DEPENDENT LATERAL TRANSFER OF ASPERGILLUS FUMIGATUS IN NECROPTOTIC HUMAN MACROPHAGES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A48, ISSN: 0040-6376
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