Ca(2+) signaling; In vivo; Microglia; Peripheral inflammation; Lipopolysaccharides; Brain; Humans; Signal Transduction; Inflammation; Ca2+ signaling; Immunology; Endocrine and Autonomic Systems; Behavioral Neuroscience
Résumé :
[en] Peripheral inflammation is known to trigger a mirror inflammatory response in the brain, involving brain's innate immune cells - microglia. However, the functional phenotypes, which these cells adopt in the course of peripheral inflammation, remain obscure. In vivo two-photon imaging of microglial Ca2+ signaling as well as process motility reveals two distinct functional states of cortical microglia during a lipopolysaccharide-induced peripheral inflammation: an early "sensor state" characterized by dramatically increased intracellular Ca2+ signaling but ramified morphology and a later "effector state" characterized by slow normalization of intracellular Ca2+ signaling but hypertrophic morphology, substantial IL-1β production in a subset of cells as well as increased velocity of directed process extension and loss of coordination between individual processes. Thus, lipopolysaccharide-induced microglial Ca2+ signaling might represent the central element connecting receptive and executive functions of microglia.
Disciplines :
Neurologie
Auteur, co-auteur :
Riester, Karin; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Brawek, Bianca; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Savitska, Daria; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Fröhlich, Nicole; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Zirdum, Elizabeta; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Mojtahedi, Nima; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
HENEKA, Michael ; Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn, Bonn, Germany, German Center for Neurodegenerative Diseases, Bonn, Germany
Garaschuk, Olga; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany. Electronic address: olga.garaschuk@uni-tuebingen.de
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
In vivo characterization of functional states of cortical microglia during peripheral inflammation.
We thank A. Weible, G. Heck, and K. Schöntag for technical assistance. This work was partially supported by VolkswagenStiftung Grant 90233 to O.G. Appendix A
Askew, K., Li, K., Olmos-Alonso, A., Garcia-Moreno, F., Liang, Y., Richardson, P., Tipton, T., Chapman, M.A., Riecken, K., Beccari, S., Sierra, A., Molnar, Z., Cragg, M.S., Garaschuk, O., Perry, V.H., Gomez-Nicola, D., Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Rep. 18 (2017), 391–405.
Avignone, E., Lepleux, M., Angibaud, J., Nagerl, U.V., Altered morphological dynamics of activated microglia after induction of status epilepticus. J. Neuroinflammation, 12, 2015, 202.
Avignone, E., Ulmann, L., Levavasseur, F., Rassendren, F., Audinat, E., Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling. J. Neurosci. 28 (2008), 9133–9144.
Bader, M.F., Taupenot, L., Ulrich, G., Aunis, D., Ciesielski-Treska, J., Bacterial endotoxin induces [Ca2+]i transients and changes the organization of actin in microglia. Glia 11 (1994), 336–344.
Banks, W.A., The blood-brain barrier in neuroimmunology: tales of separation and assimilation. Brain. Behav. Immun. 44 (2015), 1–8.
Biesmans, S., Meert, T.F., Bouwknecht, J.A., Acton, P.D., Davoodi, N., De Haes, P., Kuijlaars, J., Langlois, X., Matthews, L.J., Ver Donck, L., Hellings, N., Nuydens, R., Systemic immune activation leads to neuroinflammation and sickness behavior in mice. Mediators Inflamm., 2013, 2013, 271359.
Boddeke, E.W., Meigel, I., Frentzel, S., Gourmala, N.G., Harrison, J.K., Buttini, M., Spleiss, O., Gebicke-Harter, P., Cultured rat microglia express functional beta-chemokine receptors. J. Neuroimmunol. 98 (1999), 176–184.
Brawek, B., Garaschuk, O., 2019. Single-cell electroporation for measuring in vivo calcium dynamics in microglia. In: Garaschuk, O., Verkhrasky, A. (Eds.), Microglia: Methods and Protocols. Springer Science and Business Media, pp. 231–241.
Brawek, B., Liang, Y., Savitska, D., Li, K., Fomin-Thunemann, N., Kovalchuk, Y., Zirdum, E., Jakobsson, J., Garaschuk, O., A new approach for ratiometric in vivo calcium imaging of microglia. Sci. Rep., 7, 2017, 6030.
Brawek, B., Olmedillas Del Moral, M., Garaschuk, O., 2019. In vivo visualization of microglia using tomato lectin. In: Garaschuk, O., Verkhratsky, A. (Eds.), Microglia: Methods and Protocols. Springer Science and Business Media, pp. 165–175.
Brawek, B., Schwendele, B., Riester, K., Kohsaka, S., Lerdkrai, C., Liang, Y., Garaschuk, O., Impairment of in vivo calcium signaling in amyloid plaque-associated microglia. Acta Neuropathol. 127 (2014), 495–505.
Brough, D., Le Feuvre, R.A., Wheeler, R.D., Solovyova, N., Hilfiker, S., Rothwell, N.J., Verkhratsky, A., Ca2+ stores and Ca2+ entry differentially contribute to the release of IL-1 β and IL-1α from murine macrophages. J. Immunol. 170 (2003), 3029–3036.
Cazareth, J., Guyon, A., Heurteaux, C., Chabry, J., Petit-Paitel, A., Molecular and cellular neuroinflammatory status of mouse brain after systemic lipopolysaccharide challenge: importance of CCR2/CCL2 signaling. J. Neuroinflammation, 11, 2014, 132.
Chen, Z., Jalabi, W., Shpargel, K.B., Farabaugh, K.T., Dutta, R., Yin, X., Kidd, G.J., Bergmann, C.C., Stohlman, S.A., Trapp, B.D., Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. J. Neurosci. 32 (2012), 11706–11715.
Colombo, E., Farina, C., Astrocytes: key regulators of neuroinflammation. Trends Immunol. 37 (2016), 608–620.
Cunningham, C., Wilcockson, D.C., Campion, S., Lunnon, K., Perry, V.H., Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J. Neurosci. 25 (2005), 9275–9284.
Dantzer, R., O'Connor, J.C., Freund, G.G., Johnson, R.W., Kelley, K.W., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9 (2008), 46–56.
Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L., Gan, W.B., ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8 (2005), 752–758.
Deczkowska, A., Keren-Shaul, H., Weiner, A., Colonna, M., Schwartz, M., Amit, I., Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell 173 (2018), 1073–1081.
Eichhoff, G., Brawek, B., Garaschuk, O., Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo. Biochim. Biophys. Acta 1813 (2011), 1014–1024.
Elliott, E.I., Sutterwala, F.S., Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol. Rev. 265 (2015), 35–52.
Eriksson, C., Nobel, S., Winblad, B., Schultzberg, M., Expression of interleukin 1 α and β, and interleukin 1 receptor antagonist mRNA in the rat central nervous system after peripheral administration of lipopolysaccharides. Cytokine 12 (2000), 423–431.
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M.P., Invidia, L., Celani, L., Scurti, M., Cevenini, E., Castellani, G.C., Salvioli, S., Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128 (2007), 92–105.
Fuger, P., Hefendehl, J.K., Veeraraghavalu, K., Wendeln, A.C., Schlosser, C., Obermuller, U., Wegenast-Braun, B.M., Neher, J.J., Martus, P., Kohsaka, S., Thunemann, M., Feil, R., Sisodia, S.S., Skodras, A., Jucker, M., Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging. Nat. Neurosci. 20:10 (2017), 1371–1376.
Fukushima, S., Furube, E., Itoh, M., Nakashima, T., Miyata, S., Robust increase of microglia proliferation in the fornix of hippocampal axonal pathway after a single LPS stimulation. J. Neuroimmunol. 285 (2015), 31–40.
Furube, E., Kawai, S., Inagaki, H., Takagi, S., Miyata, S., Brain region-dependent heterogeneity and dose-dependent difference in transient microglia population increase during lipopolysaccharide-induced inflammation. Sci. Rep., 8, 2018, 2203.
Garaschuk, O., Milos, R.I., Konnerth, A., Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo. Nat. Protoc. 1 (2006), 380–386.
Goghari, V., Franciosi, S., Kim, S.U., Lee, Y.B., McLarnon, J.G., Acute application of interleukin-1β induces Ca2+ responses in human microglia. Neurosci. Lett. 281 (2000), 83–86.
Gustin, A., Kirchmeyer, M., Koncina, E., Felten, P., Losciuto, S., Heurtaux, T., Tardivel, A., Heuschling, P., Dostert, C., NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes. PLoS One, 10, 2015, e0130624.
Gyoneva, S., Davalos, D., Biswas, D., Swanger, S.A., Garnier-Amblard, E., Loth, F., Akassoglou, K., Traynelis, S.F., Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia 62 (2014), 1345–1360.
Hanisch, U.K., Kettenmann, H., Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10 (2007), 1387–1394.
Heneka, M.T., McManus, R.M., Latz, E., Inflammasome signalling in brain function and neurodegenerative disease. Nat. Rev. Neurosci. 19 (2018), 610–621.
Hirasawa, T., Ohsawa, K., Imai, Y., Ondo, Y., Akazawa, C., Uchino, S., Kohsaka, S., Visualization of microglia in living tissues using Iba1-EGFP transgenic mice. J. Neurosci. Res. 81 (2005), 357–362.
Hoffmann, A., Kann, O., Ohlemeyer, C., Hanisch, U.K., Kettenmann, H., Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function. J. Neurosci. 23 (2003), 4410–4419.
Hoogland, I.C., Houbolt, C., van Westerloo, D.J., van Gool, W.A., van de Beek, D., Systemic inflammation and microglial activation: systematic review of animal experiments. J. Neuroinflammation, 12, 2015, 114.
Hooper, C., Taylor, D.L., Pocock, J.M., Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes. J. Neurochem. 92 (2005), 1363–1376.
Jangula, A., Murphy, E.J., Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha-synuclein expression. Neurosci. Lett. 551 (2013), 23–27.
Jensen, C.J., Massie, A., De Keyser, J., Immune players in the CNS: the astrocyte. J. Neuroimmune Pharmacol. 8 (2013), 824–839.
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M.J., Kreutzberg, G.W., Sher, A., Littman, D.R., Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell Biol. 20 (2000), 4106–4114.
Kanneganti, T.D., Ozoren, N., Body-Malapel, M., Amer, A., Park, J.H., Franchi, L., Whitfield, J., Barchet, W., Colonna, M., Vandenabeele, P., Bertin, J., Coyle, A., Grant, E.P., Akira, S., Nunez, G., Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440 (2006), 233–236.
Kettenmann, H., Hanisch, U.K., Noda, M., Verkhratsky, A., Physiology of microglia. Physiol. Rev. 91 (2011), 461–553.
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B.V., Jacobson, K.A., Kohsaka, S., Inoue, K., UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446 (2007), 1091–1095.
Konsman, J.P., Kelley, K., Dantzer, R., Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1β and inducible nitric oxide synthase in rat brain. Neuroscience 89 (1999), 535–548.
Kovalchuk, Y., Homma, R., Liang, Y., Maslyukov, A., Hermes, M., Thestrup, T., Griesbeck, O., Ninkovic, J., Cohen, L.B., Garaschuk, O., In vivo odourant response properties of migrating adult-born neurons in the mouse olfactory bulb. Nat. Commun., 6, 2015, 6349.
Kozlowski, C., Weimer, R.M., An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo. PLoS One, 7, 2012, e31814.
Lee, G.S., Subramanian, N., Kim, A.I., Aksentijevich, I., Goldbach-Mansky, R., Sacks, D.B., Germain, R.N., Kastner, D.L., Chae, J.J., The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature 492 (2012), 123–127.
Lee, S.C., Liu, W., Dickson, D.W., Brosnan, C.F., Berman, J.W., Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 β. J. Immunol. 150 (1993), 2659–2667.
Lucas, S.M., Rothwell, N.J., Gibson, R.M., The role of inflammation in CNS injury and disease. Br. J. Pharmacol. 147:Suppl. 1 (2006), S232–S240.
Madry, C., Attwell, D., Receptors, ion channels, and signaling mechanisms underlying microglial dynamics. J. Biol. Chem. 290 (2015), 12443–12450.
Moller, T., Hanisch, U.K., Ransom, B.R., Thrombin-induced activation of cultured rodent microglia. J. Neurochem. 75 (2000), 1539–1547.
Murakami, T., Ockinger, J., Yu, J., Byles, V., McColl, A., Hofer, A.M., Horng, T., Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc. Natl. Acad. Sci. U.S.A. 109 (2012), 11282–11287.
Netea, M.G., Balkwill, F., Chonchol, M., Cominelli, F., Donath, M.Y., Giamarellos-Bourboulis, E.J., Golenbock, D., Gresnigt, M.S., Heneka, M.T., Hoffman, H.M., Hotchkiss, R., Joosten, L.A.B., Kastner, D.L., Korte, M., Latz, E., Libby, P., Mandrup-Poulsen, T., Mantovani, A., Mills, K.H.G., Nowak, K.L., O'Neill, L.A., Pickkers, P., van der Poll, T., Ridker, P.M., Schalkwijk, J., Schwartz, D.A., Siegmund, B., Steer, C.J., Tilg, H., van der Meer, J.W.M., van de Veerdonk, F.L., Dinarello, C.A., A guiding map for inflammation. Nat. Immunol. 18 (2017), 826–831.
Norden, D.M., Trojanowski, P.J., Villanueva, E., Navarro, E., Godbout, J.P., Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia 64 (2016), 300–316.
Olmedillas Del Moral, M., Asavapanumas, N., Uzcategui, N.L., Garaschuk, O., 2019. Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo. Int. J. Mol. Sci. 20(3). pii: E589.
Pasparakis, M., Alexopoulou, L., Episkopou, V., Kollias, G., Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J. Exp. Med. 184 (1996), 1397–1411.
Pozner, A., Xu, B., Palumbos, S., Gee, J.M., Tvrdik, P., Capecchi, M.R., Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse. Front. Mol. Neurosci., 8, 2015, 12.
Qin, L., He, J., Hanes, R.N., Pluzarev, O., Hong, J.S., Crews, F.T., Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment. J. Neuroinflammation, 5, 2008, 10.
Schwendele, B., Brawek, B., Hermes, M., Garaschuk, O., High resolution in vivo imaging of microglia using a versatile non genetically-encoded marker. Eur. J. Immunol. 42 (2012), 2193–2196.
Shankaran, M., Marino, M.E., Busch, R., Keim, C., King, C., Lee, J., Killion, S., Awada, M., Hellerstein, M.K., Measurement of brain microglial proliferation rates in vivo in response to neuroinflammatory stimuli: application to drug discovery. J. Neurosci. Res. 85 (2007), 2374–2384.
Sousa, C., Golebiewska, A., Poovathingal, S.K., Kaoma, T., Pires-Afonso, Y., Martina, S., Coowar, D., Azuaje, F., Skupin, A., Balling, R., Biber, K., Niclou, S.P., Michelucci, A., 2018. Single-cell transcriptomics reveals distinct inflammation-induced microglia signatures. EMBO Rep. 19.
Stosiek, C., Garaschuk, O., Holthoff, K., Konnerth, A., In vivo two-photon calcium imaging of neuronal networks. Proc. Natl. Acad. Sci. U.S.A. 100 (2003), 7319–7324.
Stratoulias, V., Venero, J.L., Tremblay, M.E., Joseph, B., Microglial subtypes: diversity within the microglial community. EMBO J., 38, 2019, e101997.
Strowig, T., Henao-Mejia, J., Elinav, E., Flavell, R., Inflammasomes in health and disease. Nature 481 (2012), 278–286.
Tejera, D., Mercan, D., Sanchez-Caro, J.M., Hanan, M., Greenberg, D., Soreq, H., Latz, E., Golenbock, D., Heneka, M.T., Systemic inflammation impairs microglial Abeta clearance through NLRP3 inflammasome. EMBO J., 38, 2019, e101064.
Van Dam, A.M., Bauer, J., Tilders, F.J., Berkenbosch, F., Endotoxin-induced appearance of immunoreactive interleukin-1 beta in ramified microglia in rat brain: a light and electron microscopic study. Neuroscience 65 (1995), 815–826.
Yang, T.T., Lin, C.J., Hsu, C.T., Wang, T.F., Ke, F.Y., Kuo, Y.M., Differential distribution and activation of microglia in the brain of male C57BL/6J mice. Brain Struct. Funct. 218 (2013), 1051–1060.
Yong, V.W., Rivest, S., Taking advantage of the systemic immune system to cure brain diseases. Neuron 64 (2009), 55–60.
Zhang, J.T., Two-way MANOVA with unequal cell sizes and unequal cell covariance matrices. Technometrics 53 (2011), 426–439.
