scholarly journals The Long Pentraxin PTX3 Controls Klebsiella Pneumoniae Severe Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatemeh Asgari ◽  
Domenico Supino ◽  
Raffaella Parente ◽  
Nadia Polentarutti ◽  
Matteo Stravalaci ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Klebsiella Pneumoniae ◽  
Inflammatory Responses ◽  
Severe Infection ◽  
Multidrug Resistant ◽  
Histopathological Analysis ◽  
Independent Manner ◽  
Human Sepsis ◽  
Tnf Α

Klebsiella pneumoniae is a common pathogen in human sepsis. The emergence of multidrug-resistant K. pneumoniae strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against K. pneumoniae infections using Ptx3-/- mice and mouse models of severe K. pneumoniae infections. Local and systemic PTX3 expression was induced following K. pneumoniae pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of K. pneumoniae infection revealed that PTX3 did not interact with K. pneumoniae, or promote opsonophagocytosis. The comparison of susceptibility of wild-type, Ptx3-/-, C3-/- and Ptx3-/-/C3-/- mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in Ptx3-/- mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of K. pneumoniae infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections.

scholarly journals Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner

2009 ◽  
Vol 77 (9) ◽  
pp. 3686-3695 ◽  
Author(s):  
Hany M. Ibrahim ◽  
Hiroshi Bannai ◽  
Xuenan Xuan ◽  
Yoshifumi Nishikawa
Keyword(s):  
Nitric Oxide ◽  
Toxoplasma Gondii ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Independent Manner ◽  
Necrosis Factor Alpha ◽  
Parasite Multiplication ◽  
Factor Alpha

ABSTRACT Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide (NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.

Social Stressors, Arboviral Infection, and Immune Dysregulation in the Coastal Lowland Region of Ecuador: A Mixed Methods Approach in Ecological Perspective

2021 ◽  
Author(s):  
Denisse Vega Ocasio ◽  
Anna M. Stewart-Ibarra ◽  
Rachel Sippy ◽  
Christina Li ◽  
Kaitlyn McCue ◽  
...  
Keyword(s):  
At Risk ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Social Stressors ◽  
Biological Responses ◽  
Distress Symptoms ◽  
Tnf Α ◽  
Hair Samples ◽  
Arboviral Diseases

Aedes aegypti, the mosquito that transmits arboviral diseases such as dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV), is present in tropical and subtropical regions of the world. Individuals at risk of mosquito-borne disease (MBD) in the urban tropics face daily challenges linked to their socio-environment conditions, such as poor infrastructure, poverty, crowding, and limited access to adequate healthcare. These daily demands induce chronic stress events and dysregulated immune responses. We sought to investigate the role of socio-ecologic risk factors in distress symptoms and their impact on biological responses to MBD in Machala, Ecuador. Between 2017 and 2019, individuals (≥ 18 years) with suspected arbovirus illness (DENV, ZIKV, and CHIKV) from sentinel clinics were enrolled (index cases, N = 28). Cluster investigations of the index case households and people from four houses within a 200-m radius of index home (associate cases, N = 144) were conducted (total N = 172). Hair samples were collected to measure hair cortisol concentration (HCC) as a stress biomarker. Blood samples were collected to measure serum cytokines concentrations of IL-10, IL-8, TNF-α, and TGF-β. Univariate analyses were used to determine the association of socio-health metrics related to perceived stress scores (PSS), HCC, and immune responses. We found that housing conditions influence PSS and HCC levels in individuals at risk of MBD. Inflammatory cytokine distribution was associated with the restorative phase of immune responses in individuals with low-moderate HCC. These data suggest that cortisol may dampen pro-inflammatory responses and influence activation of the restorative phase of immune responses to arboviral infections.

3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway

2021 ◽  
pp. 074823372110394
Author(s):  
Yujing Zhang ◽  
Shuai Huang ◽  
Shiyi Tan ◽  
Mingke Chen ◽  
Shang Yang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Late Stage ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Pulmonary Inflammation ◽  
Mechanism Study ◽  
Silica Dust ◽  
Tnf Α

Occupational exposure to silica dust is related to pulmonary inflammation and silicosis. Lipopolysaccharides (LPSs) could aggravate apoptosis in alveolar macrophages (AMs) of human silicosis through autophagy, yet how the reduction of autophagy attenuated LPS-induced lung injury and the related mechanisms need to be investigated. In the study, we aim to understand the role of 3-methyladenine (3-MA), an inhibitor of autophagy, in LPS-mediated inflammatory responses and fibrosis. We collected AMs from observers/silicosis patients. The results showed that LPS induced NF-κB-related pulmonary inflammation in observers and silicosis patients, as confirmed by an increase in the expression of IL-1β, IL-6, TNF-α, and p65, which could be inhibited by 3-MA treatment. In mice models, at the early stage (7d) of silicosis, but not the late (28d) stage, blocking autophagy reversed the increased levels of IL-1β, IL-6, TNF-α, and p65 caused by LPS. Mechanism study revealed that LPS triggered the expression of LC3 II, p62, and cleaved caspase-3 at the early stage exposed to silica, which could be restored by 3-MA, while there was no difference in the expression of LAMP1 either at the early or late stage of silicosis in different groups. Similarly, 3-MA treatment did not prevent fibrosis characterized by destroyed alveoli, collagen deposition, and increased expression of α-SMA and Col-1 induced by LPS at the late stage of silicosis. The results suggested that 3-MA has a role in the protection of lung injury at the early stage of silicosis and provided an experimental basis for preventive strategies of pulmonary inflammation and silicosis.

scholarly journals Proinflammatory responses in SARS-CoV-2 infected and soluble spike glycoprotein S1 subunit activated human macrophages

2021 ◽  
Author(s):  
Kim Chiok ◽  
Kevin Hutchison ◽  
Lindsay Grace Miller ◽  
Santanu Bose ◽  
Tanya A Miura
Keyword(s):  
Virus Infection ◽  
Inflammatory Response ◽  
Virus Replication ◽  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Activated Macrophages ◽  
Human Macrophages ◽  
Tnf Α ◽  
Proinflammatory Responses

Critically ill COVID-19 patients infected with SARS-CoV-2 display signs of generalized hyperinflammation. Macrophages trigger inflammation to eliminate pathogens and repair tissue, but this process can also lead to hyperinflammation and resulting exaggerated disease. The role of macrophages in dysregulated inflammation during SARS-CoV-2 infection is poorly understood. We used SARS-CoV-2 infected and glycosylated soluble SARS-CoV-2 Spike S1 subunit (S1) treated THP-1 human-derived macrophage-like cell line to clarify the role of macrophages in pro-inflammatory responses. Soluble S1 upregulated TNF-α and CXCL10 mRNAs, and induced secretion of TNF-α from THP-1 macrophages. While THP-1 macrophages did not support productive SARS-CoV-2 replication, virus infection resulted in upregulation of both TNF-α and CXCL10 genes. Our study shows that S1 is a key viral component inducing inflammatory response in macrophages, independently of virus replication. Thus, virus-infected or soluble S1-activated macrophages may become sources of pro-inflammatory mediators contributing to hyperinflammation in COVID-19 patients.

Abstract 553: Siglec-1 (CD169) on Monocytes/Macrophages: A New Receptor For Extracellular Self-RNA in Triggering Inflammatory Responses via the Sheddase TACE/ADAM17

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
Extracellular Rna ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: –]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.

scholarly journals The role of RND-type efflux pumps in multidrug-resistant mutants of Klebsiella pneumoniae

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rui Ting Ni ◽  
Motoyasu Onishi ◽  
Minako Mizusawa ◽  
Ryoko Kitagawa ◽  
Takanori Kishino ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistant Mutants

scholarly journals Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 372 ◽  
Author(s):  
Karl J. Harber ◽  
Kyra E. de Goede ◽  
Sanne G. S. Verberk ◽  
Elisa Meinster ◽  
Helga E. de Vries ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Phenotype ◽  
Independent Manner ◽  
Inflammatory Macrophages ◽  
Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

scholarly journals Inducible Expression of Human β-Defensin 2 byFusobacterium nucleatum in Oral Epithelial Cells: Multiple Signaling Pathways and Role of Commensal Bacteria in Innate Immunity and the Epithelial Barrier

2000 ◽  
Vol 68 (5) ◽  
pp. 2907-2915 ◽  
Author(s):  
Suttichai Krisanaprakornkit ◽  
Janet R. Kimball ◽  
Aaron Weinberg ◽  
Richard P. Darveau ◽  
Brian W. Bainbridge ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cell Wall ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inducible Expression ◽  
Periodontal Pathogen ◽  
Gingival Tissue ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACT Human gingival epithelial cells (HGE) express two antimicrobial peptides of the β-defensin family, human β-defensin 1 (hBD-1) and hBD-2, as well as cytokines and chemokines that contribute to innate immunity. In the present study, the expression and transcriptional regulation of hBD-2 was examined. HBD-2 mRNA was induced by cell wall extract of Fusobacterium nucleatum, an oral commensal microorganism, but not by that of Porphyromonas gingivalis, a periodontal pathogen. HBD-2 mRNA was also induced by the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and phorbol myristate acetate (PMA), an epithelial cell activator. HBD-2 mRNA was also expressed in 14 of 15 noninflamed gingival tissue samples. HBD-2 peptide was detected by immunofluorescence in HGE stimulated with F. nucleatum cell wall, consistent with induction of the mRNA by this stimulant. Kinetic analysis indicates involvement of multiple distinct signaling pathways in the regulation of hBD-2 mRNA; TNF-α and F. nucleatum cell wall induced hBD-2 mRNA rapidly (2 to 4 h), while PMA stimulation was slower (∼10 h). In contrast, each stimulant induced interleukin 8 (IL-8) within 1 h. The role of TNF-α as an intermediary in F. nucleatum signaling was ruled out by addition of anti-TNF-α that did not inhibit hBD-2 induction. However, inhibitor studies show that F. nucleatum stimulation of hBD-2 mRNA requires both new gene transcription and new protein synthesis. Bacterial lipopolysaccharides isolated from Escherichia coli andF. nucleatum were poor stimulants of hBD-2, although they up-regulated IL-8 mRNA. Collectively, our findings show inducible expression of hBD-2 mRNA via multiple pathways in HGE in a pattern that is distinct from that of IL-8 expression. We suggest that different aspects of innate immune responses are differentially regulated and that commensal organisms have a role in stimulating mucosal epithelial cells in maintaining the barrier that contributes to homeostasis and host defense.

scholarly journals Interleukin-37: The Effect of Anti-Inflammatory Response in Human Coronary Artery Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xianfeng Yan ◽  
Bin Xie ◽  
Guihai Wu ◽  
Jing Hu ◽  
Di Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Inflammatory Response ◽  
Atherosclerotic Plaque ◽  
Inflammatory Responses ◽  
Plaque Formation ◽  
Human Coronary Artery ◽  
Atherosclerotic Plaque Formation

Interleukin-37 (IL-37) is unique in the IL-1 family since it broadly suppresses innate immunity and elevates in humans with inflammatory and autoimmune diseases. IL-37 shows definite groups and transcripts for human IL37 gene, but it is still not completely understood the effect and mechanisms of inflammatory response in endothelial cells. It is well accepted that endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation, which leads to the occurrence and development of the cardiovascular adverse events in clinical since the inflammatory responses of endothelial cells could induce and enhance the deposition of extensive lipid and the formation of atherosclerotic plaque in the intima. Thus, it is essential to investigate the role and potential mechanisms in endothelial inflammatory response to prevent the formation and development of many cardiovascular diseases including atherosclerosis. So far, the recent studies have revealed that IL-37 is able to inhibit inflammatory response by suppressing the TLR2-NF-κB-ICAM-1 pathway intracellularly in human coronary artery endothelial cells (HCAECs). Further, the role of IL-37 may be related to the IL-18 pathway extracellularly and involved in the adhesion and transmigration of neutrophils in HCAECs.

TNF-α, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity

2020 ◽  
Vol 319 (3) ◽  
pp. G281-G288 ◽  
Author(s):  
Pasquale Mansueto ◽  
Diana Di Liberto ◽  
Francesca Fayer ◽  
Maurizio Soresi ◽  
Girolamo Geraci ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Adaptive Immunity ◽  
Significant Role ◽  
Adaptive Response ◽  
Rectal Mucosa ◽  
Tnf Α ◽  
Wheat Sensitivity

Nonceliac wheat sensitivity (NCWS) is a syndrome characterized by symptoms triggered by gluten intake. The pathogenesis is still uncertain. Studies have shown a role for innate immunity. We demonstrated that production of TNF-α by CD45+, CD3+, CD4+, and CD8+ cells and of IL-17 by CD4+ cells is higher in the rectal tissue of NCWS patients than in controls. We clearly demonstrated that in patients with NCWS there is a significant role for the adaptive response.

Sign in / Sign up

Export Citation Format

Share Document