scholarly journals Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia

2019 ◽  
Vol 87 (11) ◽  
Author(s):  
Patrick Steck ◽  
Felix Ritzmann ◽  
Anja Honecker ◽  
Giovanna Vella ◽  
Christian Herr ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Interleukin 17 ◽  
Immune Functions ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Functional Receptor

ABSTRACT Neutrophils contribute to lung injury in acute pneumococcal pneumonia. The interleukin 17 receptor E (IL-17RE) is the functional receptor for the epithelial-derived cytokine IL-17C, which is known to mediate innate immune functions. The aim of this study was to investigate the contribution of IL-17RE/IL-17C to pulmonary inflammation in a mouse model of acute Streptococcus pneumoniae pneumonia. Numbers of neutrophils and the expression levels of the cytokine granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF-α) were decreased in lungs of IL-17RE-deficient (Il-17re−/−) mice infected with S. pneumoniae. Numbers of alveolar macrophages rapidly declined in both wild-type (WT) and Il-17re−/− mice and recovered 72 h after infection. There were no clear differences in the elimination of bacteria and numbers of blood granulocytes between infected WT and Il-17re−/− mice. The fractions of granulocyte-monocyte progenitors (GMPs) were significantly reduced in infected Il-17re−/− mice. Numbers of neutrophils were significantly reduced in lungs of mice deficient for IL-17C 24 h after infection with S. pneumoniae. These data indicate that the IL-17C/IL-17RE axis promotes the recruitment of neutrophils without affecting the recovery of alveolar macrophages in the acute phase of S. pneumoniae lung infection.

scholarly journals Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

2011 ◽  
Vol 79 (7) ◽  
pp. 2597-2607 ◽  
Author(s):  
Poonam Dharmani ◽  
Jaclyn Strauss ◽  
Christian Ambrose ◽  
Emma Allen-Vercoe ◽  
Kris Chadee
Keyword(s):  
Tumor Necrosis ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Mucin Secretion ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Colonic Cells ◽  
Necrosis Factor

ABSTRACTThe etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial speciesFusobacterium nucleatumis a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasiveF. nucleatumisolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only liveF. nucleatuminduced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasiveF. nucleatumisolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal thatF. nucleatummay represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

scholarly journals Enterococcus faecalisDemonstrates Pathogenicity through Increased Attachment in anEx VivoPolymicrobial Pulpal Infection

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Wayne Nishio Ayre ◽  
Genevieve Melling ◽  
Camille Cuveillier ◽  
Madhan Natarajan ◽  
Jessica L. Roberts ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Host Response ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Streptococcus Anginosus ◽  
Cell Counts ◽  
Tnf Α ◽  
Factor Alpha ◽  
Infection Types

ABSTRACTThis study investigated the host response to a polymicrobial pulpal infection consisting ofStreptococcus anginosusandEnterococcus faecalis, bacteria commonly implicated in dental abscesses and endodontic failure, using a validatedex vivorat tooth model. Tooth slices were inoculated with planktonic cultures ofS. anginosusorE. faecalisalone or in coculture atS. anginosus/E. faecalisratios of 50:50 and 90:10. Attachment was semiquantified by measuring the area covered by fluorescently labeled bacteria. Host response was established by viable histological cell counts, and inflammatory response was measured using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. A significant reduction in cell viability was observed for single and polymicrobial infections, with no significant differences between infection types (∼2,000 cells/mm2for infected pulps compared to ∼4,000 cells/mm2for uninfected pulps).E. faecalisdemonstrated significantly higher levels of attachment (6.5%) thanS. anginosusalone (2.3%) and mixed-species infections (3.4% for 50:50 and 2.3% for 90:10), with a remarkable affinity for the pulpal vasculature. Infections withE. faecalisdemonstrated the greatest increase in tumor necrosis factor alpha (TNF-α) (47.1-fold forE. faecalis, 14.6-fold forS. anginosus, 60.1-fold for 50:50, and 25.0-fold for 90:10) and interleukin 1β (IL-1β) expression (54.8-fold forE. faecalis, 8.8-fold forS. anginosus, 54.5-fold for 50:50, and 39.9-fold for 90:10) compared to uninfected samples. Immunohistochemistry confirmed this, with the majority of inflammation localized to the pulpal vasculature and odontoblast regions. Interestingly,E. faecalissupernatant and heat-killedE. faecalistreatments were unable to induce the same inflammatory response, suggestingE. faecalispathogenicity in pulpitis is linked to its greater ability to attach to the pulpal vasculature.

scholarly journals Brucella abortus Invasion of Osteocytes Modulates Connexin 43 and Integrin Expression and Induces Osteoclastogenesis via Receptor Activator of NF-κB Ligand and Tumor Necrosis Factor Alpha Secretion

2015 ◽  
Vol 84 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ayelén Ivana Pesce Viglietti ◽  
Paula Constanza Arriola Benitez ◽  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Carlos Alberto Fossati ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brucella Abortus ◽  
Connexin 43 ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Necrosis Factor

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aim of this study is to determine ifBrucella abortusinfection modifies osteocyte function. Our results indicate thatB. abortusinfection induced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatory cytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants fromB. abortus-infected osteocytes induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin (OPG), RANKL's decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants fromB. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β, and CD44 are involved in cell-cell interactions necessary for osteocyte survival.B. abortusinfection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet the expression of both Cx43 and integrins was inhibited by supernatants fromB. abortus-infected macrophages.B. abortusinfection was not capable of inducing osteocyte apoptosis. However, supernatants fromB. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taken together, our results indicate thatB. abortusinfection could alter osteocyte function, contributing to bone damage.

scholarly journals Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius

2011 ◽  
Vol 77 (13) ◽  
pp. 4681-4684 ◽  
Author(s):  
Ghalia Kaci ◽  
Omar Lakhdari ◽  
Joël Doré ◽  
S. Dusko Ehrlich ◽  
Pierre Renault ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Streptococcus Salivarius ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTStreptococcus salivariusexhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8).

scholarly journals Haemophilus ducreyi Lipooligosaccharides Induce Expression of the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase via Type I Interferons and Tumor Necrosis Factor Alpha in Human Dendritic Cells

2011 ◽  
Vol 79 (8) ◽  
pp. 3338-3347 ◽  
Author(s):  
Wei Li ◽  
Barry P. Katz ◽  
Stanley M. Spinola
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Treg Cells ◽  
Type I Interferons ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTHaemophilus ducreyicauses chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in thel-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3+regulatory T (Treg) cells. We previously found that FOXP3+Treg cells are enriched in experimental lesions and thatH. ducreyiinduced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC byH. ducreyi. Neutralizing antibodies against interferon alpha/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-α) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation.H. ducreyiculture supernatant andH. ducreyilipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-α, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-κB pathways. In addition, LOS-induced IFN-β activated the JAK-STAT pathway. Blocking the LOS/Toll-like receptor 4 (TLR4) signaling pathway greatly reducedH. ducreyi-induced IDO production. These findings indicate thatH. ducreyi-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-α-dependent mechanisms and the MAPK, NF-κB, and JAK-STAT pathways.

scholarly journals NF-κB RelA Is Required for Hepatoprotection during Pneumonia and Sepsis

2019 ◽  
Vol 87 (8) ◽  
Author(s):  
Yuri Kim ◽  
Eri Allen ◽  
Lillia A. Baird ◽  
Elise M. Symer ◽  
Filiz T. Korkmaz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Phase ◽  
Cell Activation ◽  
Phase Changes ◽  
Nkt Cell ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Hepatic Transcriptome

ABSTRACT Pneumonia and sepsis are distinct but integrally linked public health concerns. The hepatic acute-phase response (APR), which is largely dependent on transcription factors NF-κB RelA and STAT3, is a hallmark of these pathologies and other injurious conditions. Inactivation of the APR can promote liver injury, a frequently observed organ dysfunction during sepsis. However, whether or how the acute-phase changes promote liver tissue resilience during infections is unclear. To determine the hepatoprotective role of the hepatic APR, we utilized mice bearing hepatocyte-specific deletions of either RelA or STAT3. Mice were challenged intratracheally (i.t.), intravenously (i.v.), or intraperitoneally (i.p.) with Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, lipopolysaccharide (LPS), or alpha-galactosylceramide (αGalCer) to induce pneumonia, sepsis, or NKT cell activation. Liver injury was observed in RelA-null (hepRelAΔ/Δ) mice but not STAT3-null (hepSTAT3Δ/Δ) mice during pneumonia. The absence of RelA resulted in hepatotoxicity across several models of pneumonia, sepsis, and NKT cell activation. Injury was associated with increased levels of activated caspase-3 and -8 and substantial alteration of the hepatic transcriptome. Hepatotoxicity in the absence of RelA could be reversed by neutralization of tumor necrosis factor alpha (TNF-α). These results indicate the requirement of RelA-dependent inducible hepatoprotection during pneumonia and sepsis. Further, the results demonstrate that RelA-dependent gene programs are critical for maintaining liver homeostasis against TNF-α-driven immunotoxicity.

scholarly journals Effect of CARD9 Deficiency on Neutrophil-Mediated Host Defense against Pulmonary Infection with Streptococcus pneumoniae

2020 ◽  
Vol 89 (1) ◽  
pp. e00305-20
Author(s):  
Shigenari Ishizuka ◽  
Rin Yokoyama ◽  
Ko Sato ◽  
Ryuhei Shiroma ◽  
Ayako Nakahira ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Host Defense ◽  
Alveolar Macrophages ◽  
Neutrophil Migration ◽  
Pneumococcal Infection ◽  
Neutrophil Accumulation ◽  
Necrosis Factor Alpha ◽  
Chemokine Production ◽  
Lectin Receptors ◽  
Tnf Α

ABSTRACTStreptococcus pneumoniae is a major causative bacterium of community-acquired pneumonia. Dendritic cell-associated C-type lectin-2 (dectin-2), one of the C-type lectin receptors (CLRs), was previously reported to play a pivotal role in host defense against pneumococcal infection through regulating phagocytosis by neutrophils while not being involved in neutrophil accumulation. In the present study, to elucidate the possible contribution of other CLRs to neutrophil accumulation, we examined the role of caspase recruitment domain-containing protein 9 (CARD9), a common adaptor molecule for signal transduction triggered by CLRs, in neutrophilic inflammatory response against pneumococcal infection. Wild-type (WT), CARD9 knockout (KO), and dectin-2 KO mice were infected intratracheally with pneumococcus, and the infected lungs were histopathologically analyzed to assess neutrophil accumulation at 24 h postinfection. Bronchoalveolar lavage fluids (BALFs) were collected at the same time point to count the neutrophils and assess the production of inflammatory cytokines and chemokines. Neutrophil accumulation was significantly decreased in CARD9 KO mice, but not in dectin-2 KO mice. Tumor necrosis factor alpha (TNF-α), keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) production in BALFs were also attenuated in CARD9 KO mice, but not in dectin-2 KO mice. Production of TNF-α and KC by alveolar macrophages stimulated with pneumococcal culture supernatants was significantly attenuated in CARD9 KO mice, but not in dectin-2 KO mice, compared to that in each group’s respective control mice. In addition, pneumococcus-infected CARD9 KO mice showed larger bacterial burdens in the lungs than did WT mice. These data indicate that CARD9 is required for neutrophil migration after pneumococcal infection, as well as inflammatory cytokine and chemokine production by alveolar macrophages, and suggest that a CLR distinct from dectin-2 may be involved in this response.

scholarly journals THP-1 Cell Apoptosis in Response to Mycobacterial Infection

2003 ◽  
Vol 71 (1) ◽  
pp. 254-259 ◽  
Author(s):  
Carrie J. Riendeau ◽  
Hardy Kornfeld
Keyword(s):  
Alveolar Macrophages ◽  
Mycobacterial Infection ◽  
Host Cells ◽  
Tnf Receptor ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Retroviral Transduction ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We previously reported that Mycobacterium tuberculosis infection primes human alveolar macrophages (HAM) for tumor necrosis factor alpha (TNF-α)-mediated apoptosis and that macrophage apoptosis is associated with killing internalized bacilli. Virulent mycobacterial strains elicit much less apoptosis than attenuated strains, implying that apoptosis is a defense against intracellular infection. The present study evaluated the potential for phorbol myristate acetate-differentiated THP-1 cells to mimic this response of primary macrophages. Consistent with the behavior of alveolar macrophages, attenuated M. tuberculosis H37Ra and Mycobacterium bovis BCG strongly induce THP-1 apoptosis, which requires endogenous TNF. THP-1 apoptosis is associated with reduced viability of infecting BCG. In contrast, virulent wild-type M. tuberculosis H37Rv and M. bovis do not increase THP-1 apoptosis over baseline. BCG induced early activation of caspase 10 and 9, followed by caspase 3. In contrast, wild-type M. bovis infection failed to activate any caspases in THP-1 cells. BCG-induced THP-1 apoptosis is blocked by retroviral transduction with vectors expressing crmA but not bcl-2. We conclude that differentiated THP-1 cells faithfully model the apoptosis response of HAM. Analysis of the THP-1 cell response to infection with virulent mycobacteria suggests that TNF death signals are blocked proximal to initiator caspase activation, at the level of TNF receptor 1 or its associated intracytoplasmic adaptor complex. Interference with TNF death signaling may be a virulence mechanism that allows M. tuberculosis to circumvent innate defenses leading to apoptosis of infected host cells.

MMPs, IL-1, and TNF are Regulated by IL-17 in Periodontitis

2007 ◽  
Vol 86 (4) ◽  
pp. 347-351 ◽  
Author(s):  
A. Beklen ◽  
M. Ainola ◽  
M. Hukkanen ◽  
C. Gürgan ◽  
T. Sorsa ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Interleukin 17 ◽  
Periodontal Tissue ◽  
Gingival Fibroblasts ◽  
Tissue Destruction ◽  
Necrosis Factor Alpha ◽  
Regulatory Cytokine ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1β and tumor necrosis factor-alpha (TNF-α), it was hypothesized that it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1β, TNF-α, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1β and TNF-α, but it induced IL-1β and TNF-α production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine.

scholarly journals Interaction of the CD43 Sialomucin with the Mycobacterium tuberculosis Cpn60.2 Chaperonin Leads to Tumor Necrosis Factor Alpha Production

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Alvaro Torres-Huerta ◽  
Tomás Villaseñor ◽  
Angel Flores-Alcantar ◽  
Cristina Parada ◽  
Estefanía Alemán-Navarro ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Mycobacterium tuberculosis is the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) secreted by activated macrophages and lymphocytes are considered essential to contain Mycobacterium tuberculosis infection. The CD43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin Cpn60.2, facilitating mycobacterium-macrophage contact. We report here that Cpn60.2 induces both human THP-1 cells and mouse-derived bone marrow-derived macrophages (BMMs) to produce TNF-α and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-α production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-γ (PLC-γ), phosphatidylinositol 3-kinase (PI3K), p38, and Jun N-terminal protein kinase (JNK), both in BMMs and in THP-1 cells. Our data highlight the role of CD43 and Cpn60.2 in TNF-α production and underscore an important role for CD43 in the host-mycobacterium interaction.

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