scholarly journals Macrophage mediated recognition and clearance of Borrelia burgdorferi elicits MyD88-dependent and -independent phagosomal signals that contribute to phagocytosis and inflammation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sarah J. Benjamin ◽  
Kelly L. Hawley ◽  
Paola Vera-Licona ◽  
Carson J. La Vake ◽  
Jorge L. Cervantes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Borrelia Burgdorferi ◽  
Inflammatory Cell ◽  
Tlr Signaling ◽  
Cell Recruitment ◽  
Phagosomal Maturation ◽  
Bacterial Uptake ◽  
Inflammatory Cell Recruitment ◽  
Myd88 Signaling ◽  
Mediate Inflammation

Abstract Background Macrophages play prominent roles in bacteria recognition and clearance, including Borrelia burgdorferi (Bb), the Lyme disease spirochete. To elucidate mechanisms by which MyD88/TLR signaling enhances clearance of Bb by macrophages, we studied wildtype (WT) and MyD88−/−Bb-stimulated bone marrow-derived macrophages (BMDMs). Results MyD88−/− BMDMs exhibit impaired uptake of spirochetes but comparable maturation of phagosomes following internalization of spirochetes. RNA-sequencing of infected WT and MyD88−/− BMDMs identified a large cohort of differentially expressed MyD88-dependent genes associated with re-organization of actin and cytoskeleton during phagocytosis along with several MyD88-independent chemokines involved in inflammatory cell recruitment. We computationally generated networks which identified several MyD88-dependent intermediate proteins (Rhoq and Cyfip1) that are known to mediate inflammation and phagocytosis respectively. Conclusion Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances Bb uptake and clearance.

scholarly journals Macrophage mediated recognition and clearance of Borrelia burgdorferi elicits MyD88-dependent and -independent phagosomal signals that contribute to phagocytosis and inflammation

2021 ◽  
Author(s):  
Sarah Benjamin ◽  
Kelly L. Hawley ◽  
Paola Vera-Licona ◽  
Carson J. La Vake ◽  
Jorge L. Cervantes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Borrelia Burgdorferi ◽  
Inflammatory Cell ◽  
Tlr Signaling ◽  
Cell Recruitment ◽  
Phagosomal Maturation ◽  
Bacterial Uptake ◽  
Inflammatory Cell Recruitment ◽  
Myd88 Signaling ◽  
Mediate Inflammation

Abstract Background: Macrophages play prominent roles in bacteria recognition and clearance, including Borrelia burgdorferi (Bb), the Lyme disease spirochete. To elucidate mechanisms by which MyD88/TLR signaling enhances clearance of Bb by macrophages, we studied wildtype (WT) and MyD88-/- Bb-stimulated bone marrow-derived macrophages (BMDMs). Results: MyD88-/- BMDMs exhibit impaired uptake of spirochetes but comparable maturation of phagosomes following internalization of spirochetes. RNA-sequencing of infected WT and MyD88-/- BMDMs identified a large cohort of differentially expressed MyD88-dependent genes associated with re-organization of actin and cytoskeleton during phagocytosis along with several MyD88-independent chemokines involved in inflammatory cell recruitment. We computationally generated networks which identified several MyD88-dependent intermediate proteins (Rhoq and Cyfip1) that are known to mediate inflammation and phagocytosis respectively. Conclusion: Our findings show that MyD88 signaling enhances, but is not required, for bacterial uptake or phagosomal maturation and provide mechanistic insights into how MyD88-mediated phagosomal signaling enhances Bb uptake and clearance.

scholarly journals Regulation of LFA-1–dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3607-3614 ◽  
Author(s):  
Eun Young Choi ◽  
Valeria V. Orlova ◽  
Susanna C. Fagerholm ◽  
Susanna M. Nurmi ◽  
Li Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Cell ◽  
Mononuclear Phagocytes ◽  
Cell Recruitment ◽  
Β2 Integrin ◽  
Cytoplasmic Proteins ◽  
Inflammatory Cell Recruitment ◽  
And Migration

Abstract Inside-out signaling regulation of the β2-integrin leukocyte function–associated antigen-1 (LFA-1) by different cytoplasmic proteins, including 14-3-3 proteins, is essential for adhesion and migration of immune cells. Here, we identify a new pathway for the regulation of LFA-1 activity by Cbl-b, an adapter molecule and ubiquitin ligase that modulates several signaling pathways. Cbl-b−/− mice displayed increased macrophage recruitment in thioglycollate-induced peritonitis, which was attributed to Cbl-b deficiency in macrophages, as assessed by bone marrow chimera experiments. In vitro, Cbl-b−/− bone marrow–derived mononuclear phagocytes (BMDMs) displayed increased adhesion to endothelial cells. Activation of LFA-1 in Cbl-b–deficient cells was responsible for their increased endothelial adhesion in vitro and peritoneal recruitment in vivo, as the phenotype of Cbl-b deficiency was reversed in Cbl-b−/−LFA-1−/− mice. Consistently, LFA-1–mediated adhesion of BMDM to ICAM-1 but not VLA-4–mediated adhesion to VCAM-1 was enhanced by Cbl-b deficiency. Cbl-b deficiency resulted in increased phosphorylation of T758 in the β2-chain of LFA-1 and thereby in enhanced association of 14-3-3β protein with the β2-chain, leading to activation of LFA-1. Consistently, disruption of the 14-3-3/β2-integrin interaction abrogated the enhanced ICAM-1 adhesion of Cbl-b−/− BMDMs. In conclusion, Cbl-b deficiency activates LFA-1 and LFA-1–mediated inflammatory cell recruitment by stimulating the interaction between the LFA-1 β-chain and 14-3-3 proteins.

scholarly journals Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0145147 ◽  
Author(s):  
Silvia Affò ◽  
Daniel Rodrigo-Torres ◽  
Delia Blaya ◽  
Oriol Morales-Ibanez ◽  
Mar Coll ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Inflammatory Cell ◽  
Liver Inflammation ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

scholarly journals The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

2015 ◽  
Vol 59 (10) ◽  
pp. 6317-6327 ◽  
Author(s):  
Hussein Traboulsi ◽  
Alexandre Cloutier ◽  
Kumaraswamy Boyapelly ◽  
Marc-André Bonin ◽  
Éric Marsault ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Response ◽  
Lung Inflammation ◽  
Inflammatory Cell ◽  
Influenza Virus Infection ◽  
Cytokine Gene Expression ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
Anti Inflammatory

ABSTRACTThe host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

scholarly journals A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin

2007 ◽  
Vol 26 (4) ◽  
pp. 1129-1139 ◽  
Author(s):  
Valeria V Orlova ◽  
Eun Young Choi ◽  
Changping Xie ◽  
Emmanouil Chavakis ◽  
Angelika Bierhaus ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

scholarly journals Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers

2012 ◽  
Vol 130 (4) ◽  
pp. 869-876.e2 ◽  
Author(s):  
Michelle L. Hernandez ◽  
Margaret Herbst ◽  
John C. Lay ◽  
Neil E. Alexis ◽  
Willie June Brickey ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Inflammatory Cell ◽  
Endotoxin Challenge ◽  
Cell Recruitment ◽  
Asthmatic Patients ◽  
Inflammatory Cell Recruitment

scholarly journals Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11βHSD1-deficient mice post-MI

2010 ◽  
Vol 88 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Sara J. McSweeney ◽  
Patrick W.F. Hadoke ◽  
Agnieszka M. Kozak ◽  
Gary R. Small ◽  
Hiba Khaled ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Heart Function ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
Deficient Mice

scholarly journals Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: an Imaging Study

2020 ◽  
Vol 22 (5) ◽  
pp. 1324-1332
Author(s):  
Marie-Aline Neveu ◽  
Nicolas Beziere ◽  
Rolf Daniels ◽  
Caroline Bouzin ◽  
Arnaud Comment ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Lactate Production ◽  
High Rate ◽  
Metabolic Shift ◽  
Pyruvate Metabolism ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Abstract Purpose Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-13C-pyruvate magnetic resonance spectroscopy (MRS) and 19F magnetic resonance imaging (MRI), respectively. Procedure Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-13C-pyruvate into hyperpolarized 1-13C-lactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles. Results Hyperpolarized 1-13C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum transfer, which remained elevated during the progression of the disease, while 19F-MRI exhibited a gradual recruitment of phagocytic immune cells in arthritic ankles, which correlated well with the course of ankle swelling. Histopathology and IHC revealed that MCT-1 was expressed in regions with inflammatory cell recruitment, confirming the metabolic shift identified in arthritic ankles. Conclusions Our study demonstrated the presence of a very early metabolic shift in arthritic joints independent of phagocytic immune cell recruitment. Thus, hyperpolarized 1-13C-pyruvate represents a promising tracer to monitor acute arthritic joint inflammation, even with minor ankle swelling. Furthermore, translated to the clinics, these methods add a detailed characterization of disease status and could substantially support patient stratification and therapy monitoring.

scholarly journals Parenchymal Cell TNF Receptors Contribute to Inflammatory Cell Recruitment and Respiratory Failure inPneumocystis carinii-Induced Pneumonia

2008 ◽  
Vol 181 (2) ◽  
pp. 1409-1419 ◽  
Author(s):  
Gloria S. Pryhuber ◽  
Heidie L. Huyck ◽  
Samir Bhagwat ◽  
Michael A. O'Reilly ◽  
Jacob N. Finkelstein ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Inflammatory Cell ◽  
Parenchymal Cell ◽  
Tnf Receptors ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment
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