The Wellcome Trust Lecture: Inflammatory responses to filarial connective tissue parasites

Parasitology ◽  
1987 ◽  
Vol 94 (S1) ◽  
pp. S101-S122 ◽  
Author(s):  
F. Von Lichtenberg
Keyword(s):  
Connective Tissue ◽  
Immune Evasion ◽  
Tissue Damage ◽  
Evolutionary Biology ◽  
Inflammatory Responses ◽  
Onchocerca Volvulus ◽  
Disease Models ◽  
Missing Information ◽  
Schistosome Infection ◽  
Basic Principles

SUMMARYThe inflammatory responses to lymphatic filariae and to Onchocerca volvulus are reviewed with particular attention to (1) evolutionary biology; (2) inflammatory host spectrum; (3) non-specific components; (4) immunoregulation; (5) immune evasion versus immunomodulation; (6) chronic tissue damage and scarring and (7) disease models. Basic principles of pathogenesis are emphasized, comparisons drawn with schistosome infection, and critical items of missing information are highlighted.

scholarly journals Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ricardo Louzada da Silva ◽  
Diana M. Elizondo ◽  
Nailah Z. D. Brandy ◽  
Naomi L. Haddock ◽  
Thomas A. Boddie ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Inflammatory Cytokine ◽  
Leishmania Donovani ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Bone Marrow Cells ◽  
Parasitic Infections ◽  
Inflammatory Factor ◽  
Immune Functions ◽  
Inflammatory Cytokine Production

AbstractMacrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.

scholarly journals White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery

2021 ◽  
Author(s):  
Brody H Foy ◽  
Thor Sundt ◽  
Jonathan CT Carlson ◽  
Aaron D Aguirre ◽  
John M Higgins
Keyword(s):  
Relative Risk ◽  
Blood Cell ◽  
White Blood Cell ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Good Prognosis ◽  
Adverse Outcomes ◽  
Acute Phase Reactants ◽  
Risk Of Death ◽  
Relative Risk Of Death

Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends. We studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.

scholarly journals Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Coombs ◽  
Antonios Georgantzoglou ◽  
Hazel A. Walker ◽  
Julian Patt ◽  
Nicole Merten ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Tissue Damage ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Receptor Trafficking ◽  
Migratory Response ◽  
Cell Behaviors ◽  
Downstream Signaling

AbstractImmune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

scholarly journals IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xianghong Li ◽  
Wanchang Cui ◽  
Lisa Hull ◽  
Li Wang ◽  
Tianzheng Yu ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Binding Protein ◽  
Treated Group ◽  
Therapeutic Window ◽  
Mouse Serum ◽  
Mouse Heart ◽  
Cell Counts ◽  
Radiation Induced

Abstract Recent studies suggested that radiation exposure causes local and systemic inflammatory responses and induces cell and tissue damage. We have reported that IL-18 plays an important role in radiation-induced injury. Here, we demonstrate that IL-18 binding protein (IL-18BP), a natural antagonist of IL-18, was significantly increased (1.7–63 fold) in mouse serum on day 1 after 0.5–10 Gy TBI. However, this high level of IL-18BP was not sufficient to neutralize the active IL-18 in irradiated mice, resulting in a radiation dose-dependent free IL-18 increase in these mice’s serum which led to pathological alterations to the irradiated cells and tissues and finally caused animal death. Administration of recombinant human (rh) IL-18BP (1.5 mg/kg) with single (24, 48 or 72 h post-TBI) or double doses (48 h and 5 days post-TBI) subcutaneous (SC) injection increased 30-day survival of CD2F1 mice after 9 Gy TBI 12.5–25% compared with the vehicle control treated group, respectively. Furthermore, the mitigative effects of rhIL-18BP included balancing the ratio of IL-18/IL-18BP and decreasing the free IL-18 levels in irradiated mouse serum and significantly increasing blood cell counts, BM hematopoietic cellularity and stem and progenitor cell clonogenicity in mouse BM. Furthermore, IL-18BP treatment inhibited the IL-18 downstream target interferon (IFN)-γ expression in mouse BM, decreased reactive oxygen species (ROS) level in the irradiated mouse heart tissues, attenuated the stress responsive factor GDF-15 (growth differentiation factor-15) and increased the intestine protector citrulline level in total body irradiated mouse serum, implicating that IL-18BP may protect multiple organs from radiation-induced inflammation and oxidative stress. Our data suggest that IL-18 plays a key role in radiation-induced cell and tissue damage and dysfunction; and for the first time demonstrated that IL-18BP counters IL-18 activation and therefore may mitigate/treat radiation-induced multiple organ injuries and increase animal survival with a wider therapeutic window from 24 h and beyond after lethal doses of radiation exposure.

Connective Tissue Damage in Emphysema

1973 ◽  
Vol 107 (4) ◽  
pp. 589-595 ◽  
Author(s):  
W. G. Johanson ◽  
R. C. Reynolds ◽  
T. C. Scott ◽  
A. K. Pierce
Keyword(s):  
Connective Tissue ◽  
Tissue Damage

The Effect of Muscle Actions on the Level of Connective Tissue Damage

2011 ◽  
Vol 19 (4) ◽  
pp. 259-270 ◽  
Author(s):  
Antonio de C. Nogueira ◽  
Rodrigo G. S. Vale ◽  
André L. M. Gomes ◽  
Estélio H. M. Dantas
Keyword(s):  
Connective Tissue ◽  
Tissue Damage ◽  
Muscle Actions

scholarly journals A Dual Role for Macrophages in Modulating Lung Tissue Damage/Repair during L2 Toxocara canis Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 280 ◽  
Author(s):  
Berenice Faz-López ◽  
Héctor Mayoral-Reyes ◽  
Rogelio Hernández-Pando ◽  
Pablo Martínez-Labat ◽  
Derek M. McKay ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Tissue Damage ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Parasitic Infection ◽  
Toxocara Canis ◽  
Parasitic Infections ◽  
Lung Pathology ◽  
M2 Macrophages ◽  
Alternatively Activated Macrophages

Macrophages that are classically activated (M1) through the IFN-γ/STAT1 signaling pathway have a major role in mediating inflammation during microbial and parasitic infections. In some cases, unregulated inflammation induces tissue damage. In helminth infections, alternatively activated macrophages (M2), whose activation occurs mainly via the IL-4/STAT6 pathway, have a major role in mediating protection against excessive inflammation, and has been associated with both tissue repair and parasite clearance. During the lung migratory stage of Toxocara canis, the roles of M1 and M2 macrophages in tissue repair remain unknown. To assess this, we orally infected wild-type (WT) and STAT1 and STAT6-deficient mice (STAT1−/− and STAT6−/−) with L2 T. canis, and evaluated the role of M1 or M2 macrophages in lung pathology. The absence of STAT1 favored an M2 activation pattern with Arg1, FIZZ1, and Ym1 expression, which resulted in parasite resistance and lung tissue repair. In contrast, the absence of STAT6 induced M1 activation and iNOS expression, which helped control parasitic infection but generated increased inflammation and lung pathology. Next, macrophages were depleted by intratracheally inoculating mice with clodronate-loaded liposomes. We found a significant reduction in alveolar macrophages that was associated with higher lung pathology in both WT and STAT1−/− mice; in contrast, STAT6−/− mice receiving clodronate-liposomes displayed less tissue damage, indicating critical roles of both macrophage phenotypes in lung pathology and tissue repair. Therefore, a proper balance between inflammatory and anti-inflammatory responses during T. canis infection is necessary to limit lung pathology and favor lung healing.

scholarly journals Injured liver-released miRNA-122 elicits acute pulmonary inflammation via activating alveolar macrophage TLR7 signaling pathway

2019 ◽  
Vol 116 (13) ◽  
pp. 6162-6171 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Fangfang Jin ◽  
Xin Yan ◽  
Guifang Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alveolar Macrophage ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Underlying Mechanism ◽  
Causative Role ◽  
Independent Manner ◽  
Liver Injuries

Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.

scholarly journals Wound-induced Ca2+ wave propagates through a simple release and diffusion mechanism

2017 ◽  
Vol 28 (11) ◽  
pp. 1457-1466 ◽  
Author(s):  
L. Naomi Handly ◽  
Roy Wollman
Keyword(s):  
Diffusion Model ◽  
Tissue Damage ◽  
Atp Hydrolysis ◽  
Inflammatory Responses ◽  
Diffusion Mechanism ◽  
Fast Activation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
And Diffusion ◽  
Source And Sink

Damage-associated molecular patterns (DAMPs) are critical mediators of information concerning tissue damage from damaged cells to neighboring healthy cells. ATP acts as an effective DAMP when released into extracellular space from damaged cells. Extracellular ATP receptors monitor tissue damage and activate a Ca2+ wave in the surrounding healthy cells. How the Ca2+ wave propagates through cells after a wound is unclear. Ca2+ wave activation can occur extracellularly via external receptors or intracellularly through GAP junctions. Three potential mechanisms to propagate the Ca2+ wave are source and sink, amplifying wave, and release and diffusion. Both source and sink and amplifying wave regulate ATP levels using hydrolysis or secretion, respectively, whereas release and diffusion relies on dilution. Here we systematically test these hypotheses using a microfluidics assay to mechanically wound an epithelial monolayer in combination with direct manipulation of ATP hydrolysis and release. We show that a release and diffusion model sufficiently explains Ca2+-wave propagation after an epithelial wound. A release and diffusion model combines the benefits of fast activation at short length scales with a self-limiting response to prevent unnecessary inflammatory responses harmful to the organism.

scholarly journals Searching for principles of microbial physiology

2020 ◽  
Vol 44 (6) ◽  
pp. 821-844
Author(s):  
Frank J Bruggeman ◽  
Robert Planqué ◽  
Douwe Molenaar ◽  
Bas Teusink
Keyword(s):  
Experimental Data ◽  
Growth Rate ◽  
Evolutionary Biology ◽  
Current Status ◽  
Basic Principles ◽  
Future Directions ◽  
Selective Pressures ◽  
State Growth ◽  
Microbial Systems ◽  
Working Out

ABSTRACT Why do evolutionarily distinct microorganisms display similar physiological behaviours? Why are transitions from high-ATP yield to low(er)-ATP yield metabolisms so widespread across species? Why is fast growth generally accompanied with low stress tolerance? Do these regularities occur because most microbial species are subject to the same selective pressures and physicochemical constraints? If so, a broadly-applicable theory might be developed that predicts common microbiological behaviours. Microbial systems biologists have been working out the contours of this theory for the last two decades, guided by experimental data. At its foundations lie basic principles from evolutionary biology, enzyme biochemistry, metabolism, cell composition and steady-state growth. The theory makes predictions about fitness costs and benefits of protein expression, physicochemical constraints on cell growth and characteristics of optimal metabolisms that maximise growth rate. Comparisons of the theory with experimental data indicates that microorganisms often aim for maximisation of growth rate, also in the presence of stresses; they often express optimal metabolisms and metabolic proteins at optimal concentrations. This review explains the current status of the theory for microbiologists; its roots, predictions, experimental evidence and future directions.

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