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Article: The Shape of μ-How Morphological Analyses Shape the Study of Microglia.

Bosch, Lance Fredrick Pahutan / Kierdorf, Katrin

2022 Volume 16, Page(s) 942462

Abstract: Microglia, the innate immune cells of the CNS parenchyma, serve as the first line of defense in a myriad of neurodevelopmental, neurodegenerative, and neuroinflammatory conditions. In response to the peripheral inflammation, circulating mediators, and ... ...

Abstract	Microglia, the innate immune cells of the CNS parenchyma, serve as the first line of defense in a myriad of neurodevelopmental, neurodegenerative, and neuroinflammatory conditions. In response to the peripheral inflammation, circulating mediators, and other external signals that are produced by these conditions, microglia dynamically employ different transcriptional programs as well as morphological adaptations to maintain homeostasis. To understand these cells' function, the field has established a number of essential analysis approaches, such as gene expression, cell quantification, and morphological reconstruction. Although high-throughput approaches are becoming commonplace in regard to other types of analyses (e.g., single-cell scRNA-seq), a similar standard for morphological reconstruction has yet to be established. In this review, we offer an overview of microglial morphological analysis methods, exploring the advantages and disadvantages of each, highlighting a number of key studies, and emphasizing how morphological analysis has significantly contributed to our understanding of microglial function in the CNS parenchyma. In doing so, we advocate for the use of unbiased, automated morphological reconstruction approaches in future studies, in order to capitalize on the valuable information embedded in the cellular structures microglia inhabit.
Language	English
Publishing date	2022-06-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.942462
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Article ; Online: Tissue-specific macrophages: how they develop and choreograph tissue biology.

Mass, Elvira / Nimmerjahn, Falk / Kierdorf, Katrin / Schlitzer, Andreas

Nature reviews. Immunology

2023 Volume 23, Issue 9, Page(s) 563–579

Abstract: Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying cells and cell debris, immune complexes, bacteria and other waste products. Simultaneously, they produce growth factors and signalling molecules - ...

Abstract	Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying cells and cell debris, immune complexes, bacteria and other waste products. Simultaneously, they produce growth factors and signalling molecules - such activities not only promote host protection in response to invading microorganisms but are also crucial for organ development and homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, such as blood vessel formation, adipogenesis, metabolism and central and peripheral neuronal function. In parallel, novel methodologies have led to the characterization of tissue-specific macrophages, with distinct subpopulations of these cells showing different developmental trajectories, transcriptional programmes and life cycles. Here, we summarize our growing knowledge of macrophage diversity and how macrophage subsets orchestrate tissue development and function. We further interrelate macrophage ontogeny with their core functions across tissues, that is, the signalling events within the macrophage niche that may control organ functionality during development, homeostasis and ageing. Finally, we highlight the open questions that will need to be addressed by future studies to better understand the tissue-specific functions of distinct macrophage subsets.
MeSH term(s)	Humans ; Macrophages ; Phagocytosis ; Signal Transduction ; Biology
Language	English
Publishing date	2023-03-15
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-023-00848-y
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Article ; Online: Detection of G-Quadruplex DNA Structures in Macrophages.

Kastl, Melanie / Hersperger, Fabian / Kierdorf, Katrin / Paeschke, Katrin

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2713, Page(s) 453–462

Abstract: In addition to the canonical B-DNA conformation, DNA can fold into different secondary structures. Among them are G-quadruplex structures (G4s). G4 structures are very stable and can fold in specific guanine-rich regions in DNA and RNA. Different in ... ...

Abstract	In addition to the canonical B-DNA conformation, DNA can fold into different secondary structures. Among them are G-quadruplex structures (G4s). G4 structures are very stable and can fold in specific guanine-rich regions in DNA and RNA. Different in silico, in vitro, and in cellulo experiments have shown that G4 structures form so far in all tested organisms. There are over 700,000 predicted G4s in higher eukaryotes, but it is so far assumed that not all will form at the same time. Their formation is dynamically regulated by proteins and is cell type-specific and even changes during the cell cycle or during different exogenous or endogenous stimuli (e.g., infection or developmental stages) can alter the G4 level. G4s have been shown to accumulate in cancer cells where they contribute to gene expression changes and the mutagenic burden of the tumor. Specific targeting of G4 structures to impact the expression of oncogenes is currently discussed as an anti-cancer treatment. In a tumor microenvironment, not only the tumor cells will be targeted by G4 stabilization but also immune cells such as macrophages. Although G4s were detected in multiple organisms and different cell types, only little is known about their role in immune cells. Here, we provide a detailed protocol to detect G4 formation in the nucleus of macrophages of vertebrates and invertebrates by microscopic imaging.
MeSH term(s)	Animals ; G-Quadruplexes ; Macrophages ; Cell Nucleus ; Cell Cycle ; DNA/genetics
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3437-0_30
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Article ; Online: Hemocyte Nuclei Isolation from Adult Drosophila melanogaster for snRNA-seq.

Hersperger, Fabian / Kastl, Melanie / Paeschke, Katrin / Kierdorf, Katrin

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2713, Page(s) 71–79

Abstract: In adult Drosophila, most of the hemocytes are macrophage-like cells (so called plasmatocytes), which serve various functions in organ homeostasis and immune defense. Ontogeny and functions are largely conserved between vertebrate and invertebrate ... ...

Abstract	In adult Drosophila, most of the hemocytes are macrophage-like cells (so called plasmatocytes), which serve various functions in organ homeostasis and immune defense. Ontogeny and functions are largely conserved between vertebrate and invertebrate macrophages. Hence, Drosophila offers a powerful genetic toolbox to study macrophage function and genetically modulate these cells. Technological advances in high-throughput sequencing approaches allowed to give an in-depth characterization of vertebrate macrophage populations and their heterogenous composition within different organs as well as changes in disease. Embryonic and larval hemocytes in Drosophila have been recently analyzed in single-cell RNA-sequencing (scRNA-seq) approaches during infection and steady state. These analyses revealed anatomical and functional Drosophila hemocyte subtypes dedicated to specific tasks. Only recently, the Fly Cell Atlas provided a whole transcriptomic single-cell atlas via single-nuclei RNA-sequencing (snRNA-seq) of adult Drosophila including many different tissues and cell types where hemocytes were also included. Yet, a specific protocol to isolate nuclei from adult hemocytes for snRNA-seq and study these cells in different experimental conditions was not available. In this chapter, we give a detailed protocol to purify hemocyte nuclei from adult Drosophila, which can be used in subsequent analyses such as snRNA-seq.
MeSH term(s)	Animals ; Drosophila melanogaster/genetics ; RNA, Small Nuclear ; Hemocytes ; Cell Nucleus ; Drosophila
Chemical Substances	RNA, Small Nuclear
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3437-0_4
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Article ; Online: Microglial tissue surveillance: The never-resting gardener in the developing and adult CNS.

Petry, Philippe / Oschwald, Alexander / Kierdorf, Katrin

European journal of immunology

2023 Volume 53, Issue 7, Page(s) e2250232

Abstract: Immunosurveillance by microglia is a dynamic process in the central nervous system (CNS) with versatile functions to maintain tissue homeostasis and provide immune defense. A tightly controlled microglia network throughout the CNS parenchyma facilitates ... ...

Abstract	Immunosurveillance by microglia is a dynamic process in the central nervous system (CNS) with versatile functions to maintain tissue homeostasis and provide immune defense. A tightly controlled microglia network throughout the CNS parenchyma facilitates efficient immunosurveillance, where each cell guards a certain tissue territory. Each cell is constantly surveilling its environment and the surrounding cells, screening for pathogens but also removing cell debris and metabolites, grooming neighboring cells and facilitating cellular crosstalk. In the absence of inflammation, this "tissue surveillance" by microglia presents an essential process for CNS homeostasis and development. In this review, we provide a summary on different tissue surveillance functions mediated by microglia, the underlying molecular machineries, and how defects, such as genetic mutations, can alter these surveillance mechanisms and cause disease onset.
MeSH term(s)	Animals ; Adult ; Humans ; Microglia ; Central Nervous System ; Homeostasis/physiology ; Inflammation/metabolism
Language	English
Publishing date	2023-05-05
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202250232
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Zs.MG 85: Show issues

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Article: Microglia in a Dish-Which Techniques Are on the Menu for Functional Studies?

Aktories, Philipp / Petry, Philippe / Kierdorf, Katrin

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 908315

Abstract: Microglia build the first line of defense in the central nervous system (CNS) and play central roles during development and homeostasis. Indeed, they serve a plethora of diverse functions in the CNS of which many are not yet fully described and more are ... ...

Abstract	Microglia build the first line of defense in the central nervous system (CNS) and play central roles during development and homeostasis. Indeed, they serve a plethora of diverse functions in the CNS of which many are not yet fully described and more are still to be discovered. Research of the last decades unraveled an implication of microglia in nearly every neurodegenerative and neuroinflammatory disease, making it even more challenging to elucidate molecular mechanisms behind microglial functions and to modulate aberrant microglial behavior. To understand microglial functions and the underlying signaling machinery, many attempts were made to employ functional
Language	English
Publishing date	2022-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.908315
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Article ; Online: Microglia: Same same, but different.

Kierdorf, Katrin / Prinz, Marco

The Journal of experimental medicine

2019 Volume 216, Issue 10, Page(s) 2223–2225

Abstract: Microglial identity in the central nervous system (CNS) is dependent on colony stimulating factor 1 receptor (CSF-1R) signaling and its ligands IL-34 and colony stimulating factor 1 (CSF-1). In this issue ... ...

Abstract	Microglial identity in the central nervous system (CNS) is dependent on colony stimulating factor 1 receptor (CSF-1R) signaling and its ligands IL-34 and colony stimulating factor 1 (CSF-1). In this issue of
MeSH term(s)	Animals ; Interpersonal Relations ; Macrophage Colony-Stimulating Factor ; Mice ; Microglia ; Receptor, Macrophage Colony-Stimulating Factor ; Signal Transduction
Chemical Substances	Macrophage Colony-Stimulating Factor (81627-83-0) ; Receptor, Macrophage Colony-Stimulating Factor (EC 2.7.10.1)
Language	English
Publishing date	2019-09-16
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20191535
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Zs.MG 45: Show issues

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Article ; Online: CNS Macrophages and Infant Infections.

Oschwald, Alexander / Petry, Philippe / Kierdorf, Katrin / Erny, Daniel

Frontiers in immunology

2020 Volume 11, Page(s) 2123

Abstract: The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the ... ...

Abstract	The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the CNS resident immune cells gave new insights into development, maturation and function of its immune guard. Microglia and CAMs undergo essential steps of differentiation and maturation triggered by environmental factors as well as intrinsic transcriptional programs throughout embryonic and postnatal development. These shaping steps allow the macrophages to adapt to their specific physiological function as first line of defense of the CNS and its interfaces. During infancy, the CNS might be targeted by a plethora of different pathogens which can cause severe tissue damage with potentially long reaching defects. Therefore, an efficient immune response of infant CNS macrophages is required even at these early stages to clear the infections but may also lead to detrimental consequences for the developing CNS. Here, we highlight the recent knowledge of the infant CNS immune system during embryonic and postnatal infections and the consequences for the developing CNS.
MeSH term(s)	Animals ; Candidiasis/embryology ; Candidiasis/immunology ; Central Nervous System/embryology ; Central Nervous System/growth & development ; Central Nervous System/immunology ; Cytokines/immunology ; Encephalomyelitis/immunology ; Female ; Fetal Diseases/immunology ; Fetus/immunology ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Macrophages/immunology ; Maternal-Fetal Exchange ; Placenta/physiology ; Pregnancy ; Pregnancy Complications, Infectious/immunology ; Prenatal Exposure Delayed Effects ; Rats ; Receptors, Pattern Recognition/immunology ; Streptococcal Infections/embryology ; Streptococcal Infections/immunology ; Toxoplasmosis, Congenital/immunology ; Virus Diseases/embryology ; Virus Diseases/immunology
Chemical Substances	Cytokines ; Receptors, Pattern Recognition
Keywords	covid19
Language	English
Publishing date	2020-09-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.02123
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Article ; Online: Origin and Differentiation of Nerve-Associated Macrophages.

Kolter, Julia / Kierdorf, Katrin / Henneke, Philipp

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 204, Issue 2, Page(s) 271–279

Abstract: The mature peripheral nervous system is a steady network structure yet shows remarkable regenerative properties. The interaction of peripheral nerves with myeloid cells has largely been investigated in the context of damage, following trauma or infection. ...

Abstract	The mature peripheral nervous system is a steady network structure yet shows remarkable regenerative properties. The interaction of peripheral nerves with myeloid cells has largely been investigated in the context of damage, following trauma or infection. Recently, specific macrophages dedicated to homeostatic peripheral nerves have come into focus. These macrophages are defined by tissue and nerve type, are seeded in part prenatally, and self-maintain via proliferation. Thus, they are markedly distinct from monocyte-derived macrophages invading after local disturbance of nerve integrity. The phenotypic and transcriptional adaptation of macrophages to the discrete nervous niche may exert axon guidance and nerve regeneration and thus contribute to the stability of the peripheral nervous network. Deciphering these conserved macrophage-nerve interactions offers new translational perspectives for chronic diseases of the peripheral nervous system, such as diabetic neuropathy and pain.
MeSH term(s)	Animals ; Cell Differentiation/immunology ; Humans ; Macrophages/cytology ; Macrophages/immunology ; Neuroimmunomodulation/immunology ; Peripheral Nerves/immunology
Language	English
Publishing date	2020-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1901077
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Zs.MG 28: Show issues

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Article: Editorial: Deciphering Phagocyte Functions Across Different Species.

Feng, Yi / Dionne, Marc S / Stamatiades, Efstathios G / Kierdorf, Katrin

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 712929

Language	English
Publishing date	2021-07-30
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.712929
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