DOCSLIB.ORG

"Macrophage Function Disorders". In: Encyclopedia of Life Sciences (ELS)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Macrophage Function Advanced article Disorders Article Contents . Introduction Keith M Lee, McMaster Immunology Research Centre & M. G. DeGroote Institute for . Macrophage Functions . Macrophage Phenotypic Diversity Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada . Role in Disease Charles Yin, McMaster Immunology Research Centre & M. G. DeGroote Institute for Infectious . Primary Immunodeficiencies in Macrophage Function Disease Research, McMaster University, Hamilton, Ontario, Canada . Concluding Remarks Chris P Verschoor, McMaster Immunology Research Centre & M. G. DeGroote Institute for Online posting date: 20th September 2013 Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada Dawn ME Bowdish, McMaster Immunology Research Centre & M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada Based in part on the previous version of this eLS article ‘Macrophage Function Disorders’ (2009) by Dawn ME Bowdish and Siamon Gordon. Macrophages are sentinel cells of the innate immune tissue microenvironment and can change considerably response. Macrophages recognise pathogen-associated with exposure to infectious and antigenic agents. They are molecular patterns (e.g. microbial products) and endo- relatively long-lived, biosynthetically active cells and genous ligands (e.g. apoptotic cells) through a broad and express diverse surface receptors and secretory products. They adapt readily to changes in their milieu and help to adaptable range of pattern-recognition receptors. The maintain homoeostasis locally and systemically. If unable consequence of this recognition is generally effective to deal adequately with an infectious or injurious stimulus, clearance via phagocytosis; however, when this is not macrophages initiate a chronic inflammatory process, effective, macrophages may become inappropriately which can contribute to persistent tissue damage; they can activated and initiate an inappropriate inflammatory also mediate acute, sometimes massive, responses from response. Because macrophages are extremely variable in other cell types and organ systems (Mukhopadhyay et al., phenotype and function and share a common ancestry with 2009). monocytes and dendritic cells, there are very few genes Although primary deficiencies of macrophage function that are expressed exclusively in macrophages. Conse- in human disease are relatively uncommon, macrophages quently, macrophage-specific immunodeficiencies are contribute to, and play a central role in, many major rare. There are, however, a number of genetic immunode- disease processes. These include storage diseases, chronic infections and immunological disorders, as well as ficiencies that affect macrophage function. In addition, as responses to metabolic injury (Table 1). Macrophages may macrophages are exquisitely attuned to their micro- participate in the pathology of disease by producing environment, their function appears to be adversely affec- secretory products or by altering functional phenotype, ted by and contributes to chronic inflammatory conditions which can be characterised by changes in the expression of such as cancer, atherosclerosis and obesity. Thus, genetic their receptors (for further information see Taylor et al. deficiencies, in addition to microenvironmental dysregu- (2005)). Herein the authors discuss a subset of macrophage lation, can contribute to macrophage function disorders. functions, focussing especially on their role in infectious and chronic diseases, and highlight the recent advances in human genetics that contribute to our understanding of Introduction macrophage function disorders. See also: Inflammation: Chronic; Macrophages Macrophages are a heterogenous family of cells whose phenotype and function depend considerably on their Macrophage Functions eLS subject area: Immunology In 1883, Ellie Metchnikoff described highly motile, amoe- How to cite: boid-like cells that were associated with phagocytosis or Lee, Keith M; Yin, Charles; Verschoor, Chris P; and Bowdish, Dawn ME ‘eating’ particulates of either exogenous (e.g. bacterial) or (September 2013) Macrophage Function Disorders. In: eLS. John Wiley endogenous (e.g. damaged host cells) origin (Metschnikoff, & Sons, Ltd: Chichester. 1884). Since then it has become clear that the diversity DOI: 10.1002/9780470015902.a0002174.pub3 of macrophage function is dazzling and includes such eLS & 2013, John Wiley & Sons, Ltd. www.els.net 1 Macrophage Function Disorders Table 1 Diseases in which macrophages play a significant role Type Example Mechanism 1. Storage Gauche’s disease Genetic lysosomal hydrolase deficiency Haemosiderosis Secondary Fe2+ accumulation in reticuloendothelial system Hasmochromatosis Primary Fe2+ overload (also other tissues) 2. Chronic Silicosis and asbestosis Nondegradable, bioactive particle accumulation in the lungs inflammation and the pleura Rheumatoid arthritis Autoimmune destruction Inflammatory bowel disease Defects in intracellular sensing of bacteria lead to a skewed cytokine response 3. Infection Septic shock (Gram-negative Release of vasoactive mediators and cytokines, especially and -positive) tumour necrosis factor a and interleukin 1b Tuberculosis Cellular immunity activates MØ, via interferon g Malaria Uptake of parasitised erythrocytes and release of mediators Acquired immune deficiency Human immunodeficiency virus infects M0 and CD4 T cells syndrome leading to failure of cellular immunity Dengue virus Antibody-dependent enhancement leads to increased infection of FcgR-expressing cells 4. Metabolic injury Atherosclerosis Oxidised lipopratelns induce foam cell formation in major arteries Alzheimer disease Nondegradable amyloid peptide induces MØ secretion of neuratoxic products 5. Malignancy Cancer Mfp within the tumour microenvironment facilitate angiogenesis, extracellular-matrix remodelling and promote tumour cell motility disparate activities as memory generation (Derecki et al., can similarly be recognised by PRRs, and are known as 2011), thermoregulation (Nguyen et al., 2011) and danger-associated molecular patterns (DAMPs). Detec- embryonic development (Hopkinson-Woolley et al., 1994). tion of PAMPs or DAMPs by PRRs activates signalling Generally speaking, macrophages have two major func- cascades that induce the production of proinflammatory tions, phagocytosis (and subsequent processing of inter- molecules and ultimately activation and maturation of the nalised matter) (Whelan et al., 2012) and production of macrophage (Mukhopadhyay et al., 2009). See also: Innate proinflammatory, antiinflammatory and angiogenic fac- Immune Mechanisms: Nonself Recognition tors such as cytokines. These two functions are essential for PRRs are expressed both on the cell surface and intra- both host defence and homoeostasis and require plasma cellularly (Figure 1). Intracellular PRRs can be localised to membrane and cytosolic pattern-recognition receptors either the endosomes or to the cytosol, allowing macro- (PRRs). phages to recognise both extracellular and intracellular PAMPs. Three broad classes of PRRs exist, namely toll- Pattern recognition like receptors (TLRs), nucleotide-binding domain and leucine-rich repeat (LRR) containing receptors (NLRs), Macrophages bind and phagocytose microbes and parti- and retinoic acid-inducible gene I-like receptors (RLRs). culates, and initiate inflammatory responses that recruit Genetic studies in mice and rare cases of mutations in leucocytes to a site of infection or tissue damage. This humans have demonstrated that these receptors are vital response is mediated by proinflammatory cytokines and for the host defence against infectious diseases. As such, chemokines produced by macrophages following pathogen mutations and polymorphisms in PRR genes can con- or danger signal recognition. Macrophages express a tribute to autoimmune disorders, chronic inflammatory variety of PRRs that are able to recognise conserved conditions and conditions such as septic shock, in which an molecular patterns, both pathogenic and harmless. Mole- overactive immune response can lead to death. See also: cular patterns derived from microbes and viruses, such as Pattern Recognition Receptor bacterial cell wall components and viral deoxyribonucleic acid/ribonucleic acid (DNA/RNA) sequences, are known as pathogen-associated molecular patterns (PAMPs), or TLRs microbe-associated molecular patterns as these conserved TLRs recognise a broad range of microbial products, host- components are not unique to pathogens. Host molecules derived molecules and synthetic agents (Table 2; Kawai and that are indicative of tissue injury, including heat shock Akira, 2010). The 13 known mammalian TLRs (10 human proteins and extracellular adenosine triphosphate (ATP), and 13 mouse) can be divided into those found 2 eLS & 2013, John Wiley & Sons, Ltd. www.els.net TLR5 TLR10 TLR4 TLR2/6 TLR11 TLR12 TLR1/2 MD2 MD2 MAL MyD88 MyD88 MAL MyD88 MyD88 MAL MyD88 Translocate MyD88 MAL MAL MyD88 (PI3K) MyD88 MAL Inflammasomes eLS Endosome & IRAKs 2013, John Wiley & Sons, Ltd. www.els.net NOD1 TRAF6 ASC NOD2 ASC PYD TLR7 TLR8 TLR9 TLR3 TLR13 Pro-caspase-1 Pro-caspase-1 TLR4 P IκB RIP2 pro-IL-1 IL-1 CARD TRIF RIP2 MyD88 pro-IL-18 IL-18 Release yD88 TRIF M NF-κB TRIF TRAM TRIF TRAM Translocate MAVS TRAF3 RIG-1 Proinflammatory IKKs κ NF- B cytokines (e.g. IL-1) P RIG-I-like receptors IRF3/7 MDA5 MAVS Antiviral/Antibacterial P Macrophage Function Disorders Translocate IRF3/7 Cytokines (e.g. IFN/) Nucleus Figure 1 Inflammatory
Load more

Recommended publications
  • Regulation of Macrophage Development and Function in Peripheral Tissues
    REVIEWS Regulation of macrophage development and function in peripheral tissues Yonit Lavin, Arthur Mortha, Adeeb Rahman and Miriam Merad Abstract | Macrophages are immune cells of haematopoietic origin that provide crucial innate immune defence and have tissue-specific functions in the regulation and maintenance of organ homeostasis. Recent studies of macrophage ontogeny, as well as transcriptional and epigenetic identity, have started to reveal the decisive role of the tissue stroma in the regulation of macrophage function. These findings suggest that most macrophages seed the tissues during embryonic development and functionally specialize in response to cytokines and metabolites that are released by the stroma and drive the expression of unique transcription factors. In this Review, we discuss how recent insights into macrophage ontogeny and macrophage–stroma interactions contribute to our understanding of the crosstalk that shapes macrophage function and the maintenance of organ integrity. Mononuclear phagocyte Macrophages are key components of the innate immune characterized the transcriptional and epigenetic pro- system system that reside in tissues, where they function as grammes of tissue-resident macrophages and revealed (MPS). A group of bone immune sentinels. They are uniquely equipped to sense the extent of diversity in these populations1,8. In addi- marrow-derived cells and respond to tissue invasion by infectious microorgan- tion to differences in ontogeny, locally derived tissue (monocytes, macrophages and isms and tissue
    [Show full text]
  • The Biochemical and Biophysical Mechanisms of Macrophage Migration
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 The Biochemical and Biophysical Mechanisms of Macrophage Migration Laurel Erin Hind University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Allergy and Immunology Commons, Biomedical Commons, Immunology and Infectious Disease Commons, and the Medical Immunology Commons Recommended Citation Hind, Laurel Erin, "The Biochemical and Biophysical Mechanisms of Macrophage Migration" (2015). Publicly Accessible Penn Dissertations. 1062. https://repository.upenn.edu/edissertations/1062 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1062 For more information, please contact [email protected]. The Biochemical and Biophysical Mechanisms of Macrophage Migration Abstract The ability of macrophages to migrate is critical for a proper immune response. During an innate immune response, macrophages migrate to sites of infection or inflammation where they clear pathogens through phagocytosis and activate an adaptive immune response by releasing cytokines and acting as antigen- presenting cells. Unfortunately, improper regulation of macrophage migration is associated with a variety of dieases including cancer, atherosclerosis, wound-healing, and rheumatoid arthritis. In this thesis, engineered substrates were used to study the chemical and physical mechanisms of macrophage migration. We first used microcontact printing to generate surfaces
    [Show full text]
  • Understanding the Immune System: How It Works
    Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them.
    [Show full text]
  • Infections Macrophage Polarization in Bacterial
    Macrophage Polarization in Bacterial Infections Marie Benoit, Benoît Desnues and Jean-Louis Mege This information is current as J Immunol 2008; 181:3733-3739; ; of September 24, 2021. doi: 10.4049/jimmunol.181.6.3733 http://www.jimmunol.org/content/181/6/3733 Downloaded from References This article cites 68 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/181/6/3733.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 24, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Macrophage Polarization in Bacterial Infections Marie Benoit, Benoît Desnues, and Jean-Louis Mege1 Converging studies have shown that M1 and M2 mac- tokines and microbial products (2). More recently, M2 macro- rophages are functionally polarized in response to mi- phages have been characterized by functional expression of al- croorganisms and host mediators. Gene expression ternative activation markers.
    [Show full text]
  • Granulocytes, Macrophages, and Dendritic Cells Arise from A
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 3038-3042, April 1993 Immunology Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow KAYO INABA*t, MUNEO INABA*, MASASHI DEGUCHI*, KATSUHIKO HAGI*, RYoJi YASUMIZUf, SUSUMU IKEHARAt, SHIGERU MURAMATSU*, AND RALPH M. STEINMAN§ *Department of Zoology, Faculty of Science, Kyoto University, Sakyo, Kyoto 606, Japan; tFirst Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570, Japan; and §Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021 Communicated by Zanvil A. Cohn, December 21, 1992 ABSTRACT The developmental origin of dendritic cells, a lineage-restricted macrophage and granulocyte colony- specialized system ofmajor histocompatibility complex (MHC) stimulating factors (M-CSF and G-CSF, respectively) (8, 10, class 11-rich antigen-presenting cells for T-celi immunity and 12). tolerance, is not well characterized. Granulocyte-macrophage Since GM-CSF can induce the formation of mixed popu- colony-stimulating factor (GM-CSF) is known to stimulate lations ofgranulocytes and macrophages in semi-solid colony dendritic cells, including growth and development from MHC systems (15), we asked whether dendritic cells could also class 11-negative precursors in suspension cultures of mouse arise from a colony-forming precursor that is common to bone marrow. Here we studied colony formation in semi-solid phagocytes. Cells with some of the features of dendritic cells methylcellulose cultures, a classical bioassay system in which have been detected in human cell colonies that were induced GM-CSF induces the formation of mixed granulocyte- with lectin-conditioned medium (16) and more recently with macrophage colonies.
    [Show full text]
  • Ornithine Decarboxylase Regulates M1 Macrophage Activation And
    Ornithine decarboxylase regulates M1 macrophage PNAS PLUS activation and mucosal inflammation via histone modifications Dana M. Hardbowera,b, Mohammad Asimb, Paula B. Luisc, Kshipra Singhb, Daniel P. Barryb, Chunying Yangd,e, Meredith A. Steevese, John L. Clevelandd,e, Claus Schneiderc, M. Blanca Piazuelob, Alain P. Gobertb, and Keith T. Wilsona,b,f,g,h,1 aDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232; bDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232; cDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232; dDepartment of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612; eDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458; fDepartment of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232; gCenter for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN 37232; and hVeterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232 Edited by Carl F. Nathan, Weill Medical College of Cornell University, New York, NY, and approved December 20, 2016 (received for review September 6, 2016) Macrophage activation is a critical step in host responses during pathogens is macrophage activation. Macrophages have the ca- bacterial infections. Ornithine decarboxylase (ODC), the rate-limiting pacity to alter cytokine/chemokine production and various other enzyme in polyamine metabolism, has been well studied in epithelial functions along the spectrum of M1 or M2 activation based on the cells and is known to have essential roles in many different cellular stimulus detected (12–14). M1 macrophages represent a highly functions. However, its role in regulating macrophage function during proinflammatory and antimicrobial subset of macrophages (12–14).
    [Show full text]
  • Cd47-Sirpα Interaction and IL-10 Constrain Inflammation-Induced Macrophage Phagocytosis of Healthy Self-Cells
    Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells Zhen Biana,b, Lei Shia, Ya-Lan Guoa, Zhiyuan Lva, Cong Tanga, Shuo Niua, Alexandra Tremblaya, Mahathi Venkataramania, Courtney Culpeppera, Limin Lib, Zhen Zhoub, Ahmed Mansoura, Yongliang Zhangc, Andrew Gewirtzd, Koby Kiddera,e, Ke Zenb, and Yuan Liua,d,1 aProgram of Immunology and Cell Biology, Department of Biology, Center for Diagnostics & Therapeutics, Georgia State University, Atlanta, GA 30302; bState Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China; cDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, Life Science Institute (LSI) Immunology Programme, National University of Singapore, Singapore 117456; dCenter for Inflammation, Immunity and Infection, Georgia State University, Atlanta, GA 30303; and eDepartment of Cell Biology, Rutgers University, New Brunswick, NJ 08901 Edited by Jason G. Cyster, University of California, San Francisco, CA, and approved July 11, 2016 (received for review October 28, 2015) − − Rapid clearance of adoptively transferred Cd47-null (Cd47 / ) cells in The CD47-SIRPα mechanism was first reported by Oldenborg congeneic WT mice suggests a critical self-recognition mechanism, et al. (1), who had demonstrated in red blood cell (RBC) in which CD47 is the ubiquitous marker of self, and its interaction transfusion experiments that WT mice rapidly eliminate syngeneic − with macrophage signal regulatory protein α (SIRPα) triggers inhib- Cd47-null (Cd47 ) RBCs through erythrophagocytosis in the itory signaling through SIRPα cytoplasmic immunoreceptor tyrosine- spleen and that the lack of tyrosine phosphorylation in SIRPα based inhibition motifs and tyrosine phosphatase SHP-1/2.
    [Show full text]
  • Monocyte and Macrophage Heterogeneity
    REVIEWS MONOCYTE AND MACROPHAGE HETEROGENEITY Siamon Gordon and Philip R. Taylor Abstract | Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. However, as we discuss here, recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues. These advances in our understanding have implications for the development of therapeutic strategies that are targeted to modify particular subpopulations of monocytes. OSTEOCLAST Circulating monocytes give rise to a variety of tissue- elicit increased recruitment of monocytes to peripheral A multinucleate cell that resident macrophages throughout the body, as well as sites4, where differentiation into macrophages and DCs resorbs bone. to specialized cells such as dendritic cells (DCs) and occurs, contributing to host defence, and tissue remod- OSTEOCLASTS. Monocytes are known to originate in the elling and repair. Studies of the mononuclear-phagocyte bone marrow from a common myeloid progenitor that system, using monoclonal antibodies specific for vari- is shared with neutrophils, and they are then released ous cell-surface receptors and differentiation antigens, into the peripheral blood, where they circulate for have shown that there is substantial heterogeneity of several days before entering tissues and replenishing phenotype, which most probably reflects the special- the tissue macrophage populations1.
    [Show full text]
  • Extracellular Polyphosphate Promotes Macrophage and Fibrocyte
    Extracellular Polyphosphate Promotes Macrophage and Fibrocyte Differentiation, Inhibits Leukocyte Proliferation, and Acts as a Chemotactic Agent for Neutrophils This information is current as of October 1, 2021. Patrick M. Suess, Luis E. Chinea, Darrell Pilling and Richard H. Gomer J Immunol published online 3 June 2019 http://www.jimmunol.org/content/early/2019/05/31/jimmun ol.1801559 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/05/31/jimmunol.180155 Material 9.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 1, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published June 3, 2019, doi:10.4049/jimmunol.1801559 The Journal of Immunology Extracellular Polyphosphate Promotes Macrophage and Fibrocyte Differentiation, Inhibits Leukocyte Proliferation, and Acts as a Chemotactic Agent for Neutrophils Patrick M. Suess,1 Luis E. Chinea, Darrell Pilling, and Richard H. Gomer Fibrocytes are monocyte-derived fibroblast like cells that participate in wound healing, but little is known about what initiates fibrocyte differentiation.
    [Show full text]
  • Exhaustion Innate Immune Suppression Rather Than
    The Journal of Immunology Acute-Phase Deaths from Murine Polymicrobial Sepsis Are Characterized by Innate Immune Suppression Rather Than Exhaustion Evan L. Chiswick,* Juan R. Mella,† John Bernardo,‡ and Daniel G. Remick* Sepsis, a leading cause of death in the United States, has poorly understood mechanisms of mortality. To address this, our model of cecal ligation and puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24 h, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, reactive oxygen species (ROS) generation, and phagocytosis. Total phagocytosis and intraphagosomal processes were deter- mined with triple-labeled Escherichia coli, covalently labeled with ROS- and pH-sensitive probes, and an ROS/pH-insensitive probe for normalization. Although similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute-phase sepsis deaths (<5 d) result from excessive inflammation, whereas chronic-phase deaths (>5 d) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first 6 h. The Journal of Immunology, 2015, 195: 3793–3802. epsis is an immune-mediated immune disorder costing so- teases (6).
    [Show full text]
  • Macrophages and Innate Immune Memory Against Staphylococcus Skin Infections COMMENTARY Jonas D
    COMMENTARY Macrophages and innate immune memory against Staphylococcus skin infections COMMENTARY Jonas D. Van Belleghema and Paul L. Bollykya,1 There is a growing appreciation that macrophages Emerging evidence suggests that innate immune contribute to innate immune memory against micro- cells, including monocytes, macrophages, and natural bial pathogens in ways that are distinct from and killer cells, might also be capable of developing complementary to adaptive immune memory. In immunological memory of previous encounters, a trait PNAS, Chan et al. (1) report that macrophages de- previously associated with the adaptive system alone. velop memory against Staphylococcus aureus skin These cell types can undergo a profound phenotypic and skin structure infections (SSSIs) and that this mem- reprogramming upon exposure to microbial stimuli ory is tissue specific and can be transferred between that influences their response to secondary infections individual animals. (12). Innate immune cells respond to microbial expo- Immune memory against S. aureus is important be- sures by increasing the expression of relevant pattern- cause of the immense impact of this microbe on hu- recognition receptors [pathogen-associated molecu- man health and because effective immunity against lar patterns (PAMPs)], thereby increasing their affinity recurrent S. aureus infections can be difficult to for particular pathogens. Called “trained immunity” achieve. S. aureus is the most common cause of skin (13), this model could conceivably include a diverse infections (2). These are often associated with massive set of epigenetic mechanisms. For example, Yoshida morbidity, mortality, and health care expenditures (3). et al. (14) demonstrated that the stress response tran- Patients often experience high rates of recurrence (4), scription factor ATF7 mediates LPS-induced epigenetic suggesting that some individuals have difficulty with changes in macrophages that lead to enhanced pro- establishing protective immunity against this organ- tection against pathogens.
    [Show full text]
  • A Novel Macrophage Subtype Directs Hematopoietic Stem Cell Homing and Retention
    79 Editorial Commentary Page 1 of 4 A novel macrophage subtype directs hematopoietic stem cell homing and retention Marcin Wysoczynski1, Joseph B. Moore IV1, Shizuka Uchida1,2 1Institute of Molecular Cardiology, Department of Medicine, 2Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, USA Correspondence to: Shizuka Uchida. Associate Professor of Medicine, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY 40202, USA. Email: [email protected]; [email protected]. Provenance: This is an invited article commissioned by the Section Editor Liuhua Zhou, MD (Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China). Comment on: Li D, Xue W, Li M, et al. VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche. Nature 2018;564:119-24. Submitted Mar 19, 2019. Accepted for publication Mar 31, 2019. doi: 10.21037/atm.2019.04.11 View this article at: http://dx.doi.org/10.21037/atm.2019.04.11 Early embryonic hematopoiesis in vertebrates proceeds in functions to actively recruit stem cells and maintain their two consecutive waves (Figure 1). The first wave, defined as plasticity throughout adulthood (2,4,5). While much is primitive hematopoiesis, takes place in the extraembryonic known regarding these processes, many of the factors which yolk sac and generates transitory hematopoietic cell compose the HSC milieu, as well as the precise signaling populations consisting of primitive erythrocytes. During events that direct HSC migration and preserve stemness, this first wave, small number of myeloid cells (e.g., primitive remain undefined. There is growing evidence that during monocytes/macrophages and megakaryocytes) are also primitive hematopoiesis in the developing embryo that generated.
    [Show full text]