scholarly journals Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Anuradha Rajamanickam ◽  
Saravanan Munisankar ◽  
Yukthi Bhootra ◽  
Chandrakumar Dolla ◽  
Thomas B. Nutman ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Acute Phase ◽  
Proinflammatory Cytokines ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Acute Phase Proteins ◽  
Strongyloides Stercoralis ◽  
Microbial Translocation ◽  
Heme Oxygenase 1 ◽  
Content Type

ABSTRACT Microbial translocation, characterized by elevated levels of lipopolysaccharide (LPS) and related markers, is a common occurrence in HIV and some parasitic infections. This is usually associated with extensive inflammation and immune activation. To examine the occurrence of microbial translocation and the associated inflammatory response in asymptomatic Strongyloides stercoralis infection, we measured the plasma levels of LPS and other microbial translocation markers, acute-phase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF]) or without (uninfected [UN]) S. stercoralis infections. Finally, we also measured the levels of all of these markers in INF individuals following treatment of S. stercoralis infection. We show that INF individuals exhibit significantly higher plasma levels of microbial translocation markers (LPS, soluble CD14 [sCD14], intestinal fatty acid-binding protein [iFABP], and endotoxin core IgG antibody [EndoCAb]), acute-phase proteins (α-2 macroglobulin [α-2M], C-reactive protein [CRP], haptoglobin, and serum amyloid protein A [SAA]), inflammatory markers (matrix metalloproteinase 1 [MMP-1] and heme oxygenase 1 [HO-1]), and proinflammatory cytokines (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], and IL-1β) than do UN individuals. INF individuals exhibit significantly decreased levels of tissue inhibitor of metalloproteinases 4 (TIMP-4). Following treatment of S. stercoralis infection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show that S. stercoralis infection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation is a feature of asymptomatic S. stercoralis infection and is associated with an inflammatory response.

scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

Mechanisms and implications of hypoalbuminemia in head-injured patients

1988 ◽  
Vol 69 (3) ◽  
pp. 386-392 ◽  
Author(s):  
Craig J. McClain ◽  
Bernhard Hennig ◽  
Linda G. Ott ◽  
Simeon Goldblum ◽  
A. Byron Young
Keyword(s):  
Endothelial Cell ◽  
Acute Phase ◽  
Nutritional Support ◽  
Cell Injury ◽  
Acute Phase Proteins ◽  
Interleukin 1 ◽  
Endothelial Permeability ◽  
Content Type ◽  
Head Injured ◽  
Injured Patients

✓ Severely head-injured patients are hypermetabolic/hypercatabolic and exhibit many aspects of the postinjury acute-phase response. These patients have hypoalbuminemia, hypozincemia, hypoferremia, hypercupria, fever, and increased synthesis of acute-phase proteins such as ceruloplasmin and higher C-reactive protein levels. It has been suggested that increased interleukin-1 (IL-1) in the ventricular fluid may be responsible, at least in part, for these metabolic abnormalities. In the present study, serum albumin levels were evaluated throughout an 18-day study period in 62 head-injured patients receiving aggressive nutritional support. Hypoalbuminemia (mean ± standard error of the mean 3.10 ± 0.2 gm/dl; normal value 3.5 to 5 gm/dl) was observed upon hospital admission; these albumin levels continued to decrease until 2 weeks postinjury, despite aggressive nutritional support. This hypoalbuminemia may be mediated via altered endothelial permeability properties due to endothelial cell dysfunction caused by cytokines such as IL-1. Transendothelial movement of albumin was assayed using a pulmonary artery endothelial cell culture system. Both a crude macrophage supernatant derived from a murine P388D cell line having IL-1 activity (mIL-1) and human recombinant IL-1 (rIL-1) were tested. The amount of albumin transferred was time- and concentration-dependent, with maximal transfer at 24 hours and 20 U of mIL-1 per 0.5 ml of culture medium. Endothelial permeability changes observed after incubation with mIL-1 were confirmed using rIL-1. Compared to control cultures, 20 U of rIL-1 and 20 U of mIL-1 increased albumin transfer across endothelial monolayers 205% and 459%, respectively. These findings suggest that the mechanism of hypoalbuminemia seen after severe head trauma can be explained in part by IL-1-induced endothelial cell injury, resulting in enhanced endothelial permeability to albumin.

scholarly journals Early-Stage Staphylococcus aureus Bloodstream Infection Causes Changes in the Concentrations of Lipoproteins and Acute-Phase Proteins and Is Associated with Low Antibody Titers against Bacterial Virulence Factors

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Stephan Michalik ◽  
Nandakumar Sundaramoorthy ◽  
Annette Murr ◽  
Maren Depke ◽  
Uwe Völker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bloodstream Infection ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
High Density Lipoproteins ◽  
Protective Function ◽  
Content Type ◽  
Early Stages ◽  
Serum Igg ◽  
Igg Binding

ABSTRACT Systemic and quantitative investigations of human plasma proteins (proteomics) and Staphylococcus aureus-specific antibodies (immunoproteomics) provide complementary information and hold promise for the discovery of biomarkers in Staphylococcus aureus bloodstream infection (SABSI). Usually, data-dependent acquisition (DDA) is used for proteome analysis of serum or plasma, but data-independent acquisition (DIA) is more comprehensive and reproducible. In this prospective cohort study, we aimed to identify biomarkers associated with the early stages of SABSI using a serum DIA proteomic and immunoproteomic approach. Sera from 49 SABSI patients and 43 noninfected controls were analyzed. In total, 608 human serum proteins were identified with DIA. A total of 386 proteins could be quantified, of which 9 proteins, mainly belonging to acute-phase proteins, were significantly increased, while 7 high-density lipoproteins were lower in SABSI. In SABSI, total anti-S. aureus serum IgG was reduced compared with controls as shown by immunoproteomic quantification of IgG binding to 143 S. aureus antigens. IgG binding to 48 of these anti-S. aureus proteins was significantly lower in SABSI, while anti-Ecb IgG was the only one increased in SABSI. Serum IgG binding to autoinducing peptide MsrB, FadB, EsxA, Pbp2, FadB, SspB, or SodA was very low in SABSI. This marker panel discriminated early SABSI from controls with 95% sensitivity and 100% specificity according to random forest prediction. This holds promise for patient stratification according to their risk of S. aureus infection, underlines the protective function of the adaptive immune system, and encourages further efforts in the development of a vaccine against S. aureus. IMPORTANCE S. aureus sepsis has a high complication and mortality rate. Given the limited therapeutic possibilities, effective prevention strategies, e.g., a vaccine, or the early identification of high-risk patients would be important but are not available. Our study showed an acute-phase response in patients with S. aureus bloodstream infection and evidence that lipoproteins are downregulated in plasma. Using immunoproteomics, stratification of patients appears to be achievable, since at the early stages of systemic S. aureus infection patients had low preexisting anti-S. aureus antibody levels. This strengthens the notion that a robust immune memory for S. aureus protects against infections with the pathogen.

scholarly journals The Invasion Plasmid Antigen J (IpaJ) from Salmonella Inhibits NF-κB Activation by Suppressing IκBα Ubiquitination

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Qiuchun Li ◽  
Lijuan Xu ◽  
Chao Yin ◽  
Zijian Liu ◽  
Yang Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Hela Cells ◽  
Salmonella Enterica ◽  
Systemic Infection ◽  
Peripheral Blood Monocyte ◽  
Effector Proteins ◽  
Economic Losses ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACT Salmonella enterica serovar Pullorum is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. In contrast to the strong inflammatory response induced by Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis, S. Pullorum causes systemic infection with little inflammation. The effector proteins secreted by Salmonella often play a crucial role in modulating host signal transduction and cellular processes to the pathogen’s advantage. In the present study, the invasion plasmid antigen J (IpaJ) protein specifically identified in S. Pullorum was found to significantly inhibit activation of the key proinflammatory transcription factor, NF-κB, which was induced by tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and lipopolysaccharide (LPS). IpaJ inhibited the NF-κB pathway in cells infected with S. Pullorum through the stabilization of IκBα. Deletion of ipaJ in S. Pullorum caused a significantly increased level of ubiquitinated IκBα that was subsequently degraded by the proteasome in HeLa cells. Moreover, IpaJ was efficient in the prevention of NF-κB translocation to the nucleus and ultimately interfered with the secretion of the proinflammatory cytokines IL-1β, IL-6, and IL-8 in infected HeLa cells. Additionally, the transformation of ipaJ into S. Enteritidis decreased the secretion of proinflammatory cytokines in HeLa cells through suppression of the NF-κB pathway. The infection of chicken peripheral blood monocyte-derived macrophages (chMDM) confirmed that ipaJ-deleted S. Pullorum induced a stronger expression of proinflammatory cytokines than the wild-type and complementary strains. In summary, the present study revealed that IpaJ functions as an important anti-inflammatory protein involved in S. Pullorum infection through inhibition of the NF-κB pathway and the subsequent inflammatory response.

Inflammation: a role for NR4A orphan nuclear receptors?

2011 ◽  
Vol 39 (2) ◽  
pp. 688-693 ◽  
Author(s):  
Jason P. McMorrow ◽  
Evelyn P. Murphy
Keyword(s):  
Inflammatory Response ◽  
Nuclear Receptors ◽  
Acute Phase ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Acute Phase Proteins ◽  
Tissue Injury ◽  
Chronic Phase ◽  
Psoriatic Skin ◽  
Orphan Nuclear Receptors

Inflammation is paradoxical; it is essential for protection following biological, chemical or physical stimuli, but inappropriate or misdirected inflammation is responsible for tissue injury in a variety of inflammatory diseases. The polarization of immune cells is critical in controlling the stages of inflammatory response. The acute phase of inflammation is characterized by a T-lymphocyte:Th2 cytokine profile and involves a co-ordinated migration of immune cells to the site of injury where production of cytokines and acute-phase proteins brings about healing. However, persistent inflammation can result in inappropriate and prolonged T-lymphocyte:Th1 cytokine-mediated action and reaction of self-molecules, leading to a chronic phase in diseases such as RA (rheumatoid arthritis), Ps (psoriasis) and atherosclerosis. The inflammatory response is also controlled by activated macrophage cells, with classically activated (M1) cells producing a wide variety of pro-inflammatory mediators, while alternatively activated (M2) macrophages participate in anti-inflammatory response. Members of the NR4A subfamily (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1) of orphan NRs (nuclear receptors) have emerged as key transcriptional regulators of cytokine and growth factor action in diseases affecting our aging population. As ligand-independent and constitutively active receptors, the activity of these transcription factors is tightly controlled at the level of expression, post-translational modification and subcellular localization. NR4A subfamily members are aberrantly expressed in inflamed human synovial tissue, psoriatic skin, atherosclerotic lesions, lung and colorectal cancer cells. Significantly, prolonged or inappropriate inflammatory responses contribute to the pathogenesis of these diseases. In activated cells, NR4A receptors are rapidly and potently induced, suggesting that these receptors may act as important transcriptional mediators of inflammatory signals. NR4A receptors may contribute to the cellular processes that control inflammation, playing a critical part in the contribution of chronic inflammation or they may have a protective role, where they may mediate pro-resolution responses. Here, we will review the contribution of the NR4A orphan NRs to integration of cytokine signalling in inflammatory disorders.

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