Evolution of Cell-Autonomous Effector Mechanisms in Macrophages versus Non-Immune Cells

Gaudet, Ryan G.; Bradfield, Clinton; MacMicking, John D.

doi:10.1128/microbiolspec.mchd-0050-2016

Cited by 18 publications

(12 citation statements)

References 228 publications

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“…1). Hence the birth of GBPs predates IFN signaling, with their primordial defense functions being refashioned in early gnathostomes (jawed vertebrates) to respond to cytokine stimulation (Kim et al, 2012; Gaudet et al, 2016; Secombes and Zou, 2017). Despite differences in inducibility, a consistent feature across most species is the expansion of GBPs into chromosomally clustered multigene families that include as many as 16 paralogues in Paramecium tetraurelia (Li et al, 2009; Shenoy et al, 2012; Fig.…”

Section: Gbps In Humans and Other Vertebratesmentioning

confidence: 99%

“…5 B). Such partners often reflect the antimicrobial machinery expressed in immune versus nonimmune cells (Gaudet et al, 2016). For example, in IFN-γ–activated mononuclear phagocytes, certain GBPs interact with the phagocyte oxidase complex (phox; NADPH oxidase) as well as proteins involved in autolysosomal killing of bacteria and inflammasome activation (Kim et al, 2011; Shenoy et al, 2012; Haldar et al, 2015; Man et al, 2016; Feeley et al, 2017).…”

Section: Gbps In Antibacterial Defensementioning

confidence: 99%

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Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

Tretina

Park

Mamińska

et al. 2019

Journal of Experimental Medicine

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209

199

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Guanylate-binding proteins (GBPs) have recently emerged as central orchestrators of immunity to infection, inflammation, and neoplastic diseases. Within numerous host cell types, these IFN-induced GTPases assemble into large nanomachines that execute distinct host defense activities against a wide variety of microbial pathogens. In addition, GBPs customize inflammasome responses to bacterial infection and sepsis, where they act as critical rheostats to amplify innate immunity and regulate tissue damage. Similar functions are becoming evident for metabolic inflammatory syndromes and cancer, further underscoring the importance of GBPs within infectious as well as altered homeostatic settings. A better understanding of the basic biology of these IFN-induced GTPases could thus benefit clinical approaches to a wide spectrum of important human diseases.

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Section: Gbps In Humans and Other Vertebratesmentioning

confidence: 99%

Section: Gbps In Antibacterial Defensementioning

confidence: 99%

Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

Tretina

Park

Mamińska

et al. 2019

Journal of Experimental Medicine

Self Cite

209

199

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“…Cell-autonomous defense mechanisms, which exist in MPS cells and also non-immune cells, provide a rapid antimicrobial response and evolved from the predator–prey relationship among the ancestors of current eukaryotes and prokaryotes ( 1 , 2 ). In MPS cells, cell-autonomous defenses include phagocytosis and autophagy, processes that originated in ancient eukaryotes for nutrient acquisition and reallocation.…”

Section: Introductionmentioning

confidence: 99%

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

et al. 2018

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The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection. In this review, we discuss the advantages and relevance of D. discoideum as a model phagocyte to study cell-autonomous defenses. We cover the antimicrobial functions of phagocytosis and autophagy and describe the processes that create a microbicidal phagosome: acidification and delivery of lytic enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+, and Fe2+ availability. High concentrations of metals poison microbes while metal sequestration inhibits their metabolic activity. We also describe microbial interference with these defenses and highlight observations made first in D. discoideum. Finally, we discuss galectins, TNF receptor-associated factors, tripartite motif-containing proteins, and signal transducers and activators of transcription, microbial restriction factors initially characterized in mammalian phagocytes that have either homologs or functional analogs in D. discoideum.

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“…Being haploid and amenable to molecular genetic techniques, Dictyostelium offers many advantages for identifying and characterizing host genes involved in resistance to pathogens (Bozzaro and Eichinger, 2011 ). Studies in the last decade have shown that Dictyostelium cells share with mammalian macrophages not only the basic phagocytic machinery, but also many mechanisms of innate and nutritional immunity (Bozzaro et al, 2008 , 2013a ; Cosson and Soldati, 2008 ; Soldati and Neyrolles, 2012 ; Nasser et al, 2013 ; Gaudet et al, 2016 ). Concerning transition metals, Dictyostelium cells share with macrophages the expression of the Nramp1 iron transporter in the phagolysosome, which is essential for proton-driven iron efflux from the phagosome, thus potentially starving bacteria for iron and manganese (Forbes and Gros, 2003 ; Courville et al, 2006 ; Peracino et al, 2006 ; Buracco et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Iron, Zinc, and Copper on Dictyostelium discoideum Cell Growth and Resistance to Legionella pneumophila

Buracco

Peracino

Andreini

et al. 2018

Front. Cell. Infect. Microbiol.

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Iron, zinc, and copper play fundamental roles in eucaryotes and procaryotes, and their bioavailability regulates host-pathogen interactions. For intracellular pathogens, the source of metals is the cytoplasm of the host, which in turn manipulates intracellular metal traffic following pathogen recognition. It is established that iron is withheld from the pathogen-containing vacuole, whereas for copper and zinc the evidence is unclear. Most infection studies in mammals have concentrated on effects of metal deficiency/overloading at organismal level. Thus, zinc deficiency or supplementation correlate with high risk of respiratory tract infection or recovery from severe infection, respectively. Iron, zinc, and copper deficiency or overload affects lymphocyte proliferation/maturation, and thus the adaptive immune response. Whether they regulate innate immunity at macrophage level is open, except for iron. The early identification in a mouse mutant susceptible to mycobacterial infection of the iron transporter Nramp1 allowed dissecting Nramp1 role in phagocytes, from the social amoeba Dictyostelium to macrophages. Nramp1 regulates iron efflux from the phagosomes, thus starving pathogenic bacteria for iron. Similar studies for zinc or copper are scant, due to the large number of copper and zinc transporters. In Dictyostelium, zinc and copper transporters include 11 and 6 members, respectively. To assess the role of zinc or copper in Dictyostelium, cells were grown under conditions of metal depletion or excess and tested for resistance to Legionella pneumophila infection. Iron shortage or overload inhibited Dictyostelium cell growth within few generations. Surprisingly, zinc or copper depletion failed to affect growth. Zinc or copper overloading inhibited cell growth at, respectively, 50- or 500-fold the physiological concentration, suggesting very efficient control of their homeostasis, as confirmed by Inductively Coupled Plasma Mass Spectrometry quantification of cellular metals. Legionella infection was inhibited or enhanced in cells grown under iron shortage or overload, respectively, confirming a major role for iron in controlling resistance to pathogens. In contrast, zinc and copper depletion or excess during growth did not affect Legionella infection. Using Zinpyr-1 as fluorescent sensor, we show that zinc accumulates in endo-lysosomal vesicles, including phagosomes, and the contractile vacuole. Furthermore, we provide evidence for permeabilization of the Legionella-containing vacuole during bacterial proliferation.

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Evolution of Cell-Autonomous Effector Mechanisms in Macrophages versus Non-Immune Cells

Cited by 18 publications

References 228 publications

Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

Differential Effects of Iron, Zinc, and Copper on Dictyostelium discoideum Cell Growth and Resistance to Legionella pneumophila

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