We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated

Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously

Pseudomonas aeruginosa is an opportunistic bacterial pathogen of plants. Unlike the well-characterized plant defense responses to highly adapted bacterial phytopathogens, little is known about plant response to P. aeruginosa infection. In this study, we examined the Brassica napus (canola) tissue-specific response to P. aeruginosa infection using RNA sequencing. Transcriptomic analysis of canola seedlings

The human pathogen Bordetella pertussis targets the respiratory epithelium and causes whooping cough. Its virulence factor adenylate cyclase toxin (CyaA) plays an important role in the course of infection. Previous studies on the impact of CyaA on human epithelial cells have been carried out using cell lines derived from the airways or the intestinal tract. Here, we investigated the interaction of

In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli-lux bioluminescence system and comparison was made at a group level between the experimental and reference

Our aim was to analyze whether endotoxemia, i.e. translocation of LPS to circulation, is reflected in the serum metabolic profile in a general population and in participants with cardiometabolic disorders. We investigated three Finnish cohorts separately and in a meta-analysis (n = 7178), namely population-based FINRISK97, FinnTwin16 consisting of young adult twins, and Parogene, a random cohort of

In response to inflammatory cytokines and chemokines, monocytes differentiate into macrophages. Comprehensive analysis of gene expression regulation of neuronal guidance cue (NGC) ligands and receptors in the monocyte-to-macrophage differentiation process is not available yet. We performed transcriptome profiling in both human primary PBMCs/PBMC-derived macrophages and THP-1 cells/THP-1-macrophages

Brucella is a genus of Gram-negative intracellular pathogens that cause animal and human diseases. Brucella survival and replication inside immune cells is critical for the establishment of chronic infections. Protein modifications by small ubiquitin-related modifier proteins and the NF-κB pathway are involved in many cellular activities, playing major roles in regulating protein function that is essential

Classical collectins (surfactant protein A and D) play a significant role in innate immunity and host defence in uropathogenic Escherichia coli (UPEC)-induced urinary tract infection (UTI). However, the functions of collectin-11 (CL-11) with respect to UPEC and UTI remain largely unexplored. This study aimed to investigate the effect of CL-11 on UPEC and its role in UTI. We further examined its modulatory

The capacity for macrophages to polarize into distinct functional activation states (e.g., M1, M2) is critical to tune an inflammatory response to the relevant infection or injury. Alternative or M2 polarization of macrophages is most often achieved in vitro in response to IL-4/IL-13 and results in the transcriptional up-regulation of a constellation of characteristic M2 marker genes. In vivo, additional

To test the dynamic changes of the expression of genes and microRNA in the gastrocnemius muscle after LPS challenge, 36 piglets were assigned to a control group (slaughtered 0 h after saline injection) and LPS groups (slaughtered at 1 h, 2 h, 4 h, 8 h, and 12 h after LPS treatment, respectively). After LPS treatment, the mRNA expression of IL-1β, IL-6, and TNF-α reached maximal levels at 1 h, 2 h,

In this study, we aim to investigate the role of miR-30a-5p in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) using LPS-induced A549 cells and mice. We found cell viability was significantly declined accompanied by cell apoptosis and cell cycle arrest at G0/G1 phase in LPS-treated A549 cells. MiR-30a-5p was down-regulated by LPS treatment and miR-30a-5p significantly protected A549

Long-chain n-3 polyunsaturated fatty acids are known to have beneficial effects on intestinal health. However, the underling mechanisms are largely unknown. The present study was conducted to investigate whether docosahexaenoic acid (DHA) attenuates TNF-α-induced intestinal cell injury and barrier dysfunction by modulating necroptosis signalling. Intestinal porcine epithelial cell line 1 was cultured

Sepsis is the major cause of mortality in the intensive care unit. The aim of this study was to identify the key prognostic biomarkers of abnormal expression and immune infiltration in sepsis. In this study, a total of 36 differentially expressed genes were identified to be mainly involved in a number of immune-related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The hub

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here,

Li S, Ojcius DM, Liao S, Li L, Xue F, Dong H and Yan J. (2010) Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin. Innate Immunity 16(2): 80–92. DOI: 10.1177/1753425909105580

The human pathogen Pseudomonas aeruginosa can rapidly induce fatal sepsis, even in previously healthy infants or children treated with appropriate antibiotics. To reduce antibiotic overuse, exploring novel complementary therapies, such as probiotics that reportedly protect patients against P. aeruginosa infection, would be particularly beneficial. However, the major mechanism underlying the clinical

As the molecular mechanisms of Brucella ovis pathogenicity are not completely clear, we have applied a transcriptome approach to identify the differentially expressed genes (DEGs) in RAW264.7 macrophage infected with B. ovis. The DEGs related to immune pathway were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis. Quantitative real-time

Modern scientific research has shown that Acanthopanax senticosus (AS) can regulate the innate immunity of healthy animals, thus affecting the health of animals. However, there are few systematic reports on the changes of innate immune indices of healthy animals after consuming AS. The purpose of this project was to study the effect on healthy mice’s innate immunity and changes of related immune factors

This study aimed to explore comprehensively the biological function of curcumin, and its underlying mechanism, in protecting from necrotising microscopic colitis in newborn rats. A total of 20 normal healthy rats were selected, and a necrotising enterocolitis (NEC) model was established. After hypoxia and hypothermia stimulation, these rats were treated with different doses of curcumin (control group

Nuclear hormone receptor ligands are known to modulate innate immunity by dampening the immune response induced by pathogens. Here, we report that unlike other ligands, 3,3′,5-triiodo-l-thyronine (T3) induced the type 1 IFN response and expression of IFN-stimulated genes (ISGs). T3 action was found to be significantly amplified at supraphysiological concentrations (SPC) and in combination with double-stranded

Spontaneous apoptosis of neutrophils plays a key role in maintaining immune homeostasis and resolving inflammation. However, the mechanism triggering this apoptosis remains obscure. In the present study, we performed a global metabolomics analysis of neutrophils undergoing spontaneous apoptosis by using hydrophilic interaction chromatography ultra-high-performance liquid chromatography-tandem quad

The blood-brain barrier (BBB), which protects the CNS from pathogens, is composed of specialized brain microvascular endothelial cells (BMECs) joined by tight junctions and ensheathed by pericytes and astrocyte endfeet. The stability of the BBB structure and function is of great significance for the maintenance of brain homeostasis. When a neurotropic virus invades the CNS via a hematogenous or non-hematogenous

Pseudomonas aeruginosa infection can induce alveolar macrophage apoptosis and autophagy, which play a vital role in eliminating pathogens. These two processes are usually not independent. Recently, autophagy has been found to interact with apoptosis during pathogen infections. Nevertheless, the role of autophagy in P. aeruginosa-infected cell apoptosis is unclear. In this study, we explored the impact

Syphilis is an important health problem worldwide; however, few studies have probed the impact of syphilitic infection on T cell turnover. The mechanisms behind the frequency of T cell subset changes and the associations between these subsets during syphilitic infection remain unclear. Herein, we used a cell-staining method and flow cytometry to explore changes in T cell subpopulations and potential

Innate immunomodulation via induction of innate memory is one mechanism to alter the host’s innate immune response to reduce or prevent disease. Microbial products modulate innate responses with immediate and lasting effects. Innate memory is characterized by enhanced (training) or depressed (tolerance) innate immune responses, including pro-inflammatory cytokine production, to secondary exposure following

Defensins are critical components of the innate immune system and play an important role in the integration of innate and adaptive immune responses. Although information on the immunomodulatory properties of peptidoglycan from bacteria is abundant, little is known about the β-defensin induction effect of peptidoglycan from the probiotic Lactobacillus. This study investigated the effect of intact peptidoglycan

Our recent study showed a high rate of HBsAg seroconversion in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To understand the immune-mediated component of the HBsAg seroconversion better, this study investigated the role of NK cells. A total of 44 IHCs were given 48 wk of PEG-IFN. Fifteen cases achieved HBsAg seroconversion (R group), whereas 29 failed (NR group). The proportion

Host response to lung infection includes coordinated efforts of multiple cell types, including the lung epithelium and macrophages. Importantly, both the lung epithelium and macrophages can internalize and clear invading pathogens. However, the mechanisms and their ability to internalize or phagocytose differ. Akt is a key cellular pathway that controls cell proliferation and survival, in addition

Psoriasis vulgaris (PsV) is an immune-mediated inflammatory disorder with devastating psychosocial consequences. Expression of immunoregulator molecules on leukocytes in PsV remains unclear. Leukocyte-associated Ig-like receptor-1 (LAIR-1) and complement receptor-1 (CR-1) are immunoregulator receptors reported to bind complement component 1q involved in phagocytosis. We aimed to explore if altered

The aberrant expression of microRNAs (miRNAs) is associated with the pathogenesis of inflammation-related diseases. However, the biological functions of miR-21 in acute lung injury (ALI) remain largely unknown. In this study, the level of miR-21 was obviously increased, but B cell lymphoma-2 (Bcl-2) expression was markedly decreased in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC)

The sensitivity of pigs to deoxynivalenol (DON) might be influenced by systemic inflammation (SI) which impacts liver. Besides following acute-phase proteins, our aim was to investigate both the hepatic fractional albumin (ALB) synthesis rate (FSR) and the ALB concentration as indicators of ALB metabolism in presence and absence of SI induced by LPS via pre- or post-hepatic venous route. Each infusion

Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal

Wang S, Deng Z, Seneviratne CJ, et al. (2015). Enterococcus faecalis promotes osteoclastogenesis and semaphorin 4D expression. Innate Immunity 21(7): 726–735. DOI: 10.1177/1753425915593162

Due to an administrative error, the articles intended for publication in the Special Issue ‘Molecular regulation of TLR signaling in health and disease’, edited by Stefanie Vogel, were published as regular articles separately from the Special Issue.

Sepsis is a life-threatening disease caused by systemic dys-regulated inflammatory response to infection. We previously revealed that LL-37, a human cathelicidin antimicrobial peptide, improves the survival of cecal ligation and puncture septic mice. Ectosomes, microvesicles released from neutrophils, are reported to be elevated in sepsis survivors; however, the functions of ectosomes in sepsis remain

Compromised TLR-mediated chronic inflammation contributes to bacterial infection-caused chronic suppurative otitis media, but the mechanisms are unclear. The present study examined the expression status of nuclear erythroid 2-related factor 2 (Nrf2) and TLRs in human middle-ear mucosae tissues collected from patients with chronic suppurative otitis media, chronic otitis media and non-otitis media,

Chorioamnionitis is associated with inflammatory end-organ damage in the fetus. Tissues in direct contact with amniotic fluid drive a pro-inflammatory response and contribute to this injury. However, due to a lack of direct contact with the amniotic fluid, the liver contribution to this response has not been fully characterized. Given its role as an immunologic organ, we hypothesized that the fetal

Berberine is an alkaloid extracted from medicinal plants such as Coptis chinensis and Phellodendron chinense. It possesses anti-inflammatory, anti-tumour and anti-oxidation properties, and regulates Glc and lipid metabolism. This study explored the mechanisms of the protective effects of berberine on barrier function and inflammatory damage in porcine intestinal epithelial cells (IPEC-J2) induced by

TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced

The cell envelope of pathogenic mycobacteria interfaces with the host. As such, the interaction of bacterial products localized at or released from the cell surface with the host’s immune system can determine the fate of the bacterium in its host. In this study, the effects of three different types of Mycobacterium bovis cell envelope fractions—purified protein derivative, total cell wall lipids and

Although liver ischaemia–reperfusion (I/R) injury remains the primary underlying reason for liver transplant failure or post-transplantation liver dysfunction, the underlying mechanism is still largely elusive. MicroRNAs (miRNA) are involved in multiple physiological and pathological processes, including inflammation. Here, we identified that the miR-128-3p/Rho family GTPase 3 (Rnd3)/NF‐κB axis might

Allergic rhinitis (AR) is a nasal mucosal inflammatory disease mediated by environmental allergens. At present, the relationship between the IL-33/ST2 axis, ERK1/2 pathway and AR progression needs further exploration. In our study, an AR model was constructed in vitro by treating HNEpC cells with Der p1. qRT-PCR was applied to assess the mRNA levels of IL-33, ST2, TNF-α, IL-6, and IL-8. Western blotting

This study aimed to investigate the possible relationship between the two biomarkers presepsin and procalcitonin (PCT) and monocyte immune function, and to explore their combination in mortality prediction in the early stage of sepsis. A total of 198 patients with bacterial infection and diagnosed with sepsis and 40 healthy control subjects were included. Blood samples were collected on admission within

TNF receptor-associated factor 6 (TRAF6) is a signal transducer, which plays a pivotal role in triggering a variety of signalling cascades. Here, we cloned and identified the TRAF6 gene from the King pigeon. The open reading frame sequence of pigeon TRAF6 (piTRAF6) is 1638 bp long and encodes a 545 aa protein, including a low-complexity domain, RING finger, Zinc finger, coiled coil domain, and meprin

Tuberculosis is one of the most common and lethal infections that afflict mankind. The study of its pathogenesis has occupied generations of investigators who have focused primarily on the role of host cellular immunity in containing the infection. Conversely, little attention has been paid to the initial stages of infection where the innate immune system’s ‘first responders’, the neutrophils, may

We aimed to discover the influence of age on the development of chronic periodontitis and illustrate the molecular mechanism in this process. Blood samples were collected from 63 chronic periodontitis patients and 30 healthy controls. Th17 cell/Foxp3+ regulatory T cell (Treg) ratio and expression of costimulatory molecules in dendritic cells (DCs) were analyzed by flow cytometry. The serum levels of

Urinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 (DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary

A subset of TLRs is specialised in the detection of incoming pathogens by sampling endosomes for nucleic acid contents. Among them, TLR3 senses the abnormal presence of double-stranded RNA in the endosomes and initiates a potent innate immune response via activation of NF-κB and IRF3. Nevertheless, mechanisms governing TLR3 regulation remain poorly defined. To identify new molecular players involved

The journal sincerely thanks the following individuals who reviewed one or more manuscripts during 2019:

Dear Editor

Dear Editor

MicroRNA (miRNA)-21 and miRNA-155 are important regulators of gene expression of different immunological molecules. This study aimed to investigate the role of miRNA-21 and miRNA-155 as biomarkers in asthma by comparing their serum expression levels in asthmatic patients to those in healthy controls and correlating their levels with serum IL-4. The expression levels of miRNA-21 and miRNA-155 were evaluated

In this study, we characterised the single exon TLR5 gene of the Chinese rural dog. Sequence analysis revealed a 2577 nucleotide-long open reading frame of canine TLR5, encoding an 858 amino acid-long protein. The putative amino acid sequence of canine TLR5 consisted of a signal peptide sequence, 15 LRR domains, a LRR C-terminal domain, a transmembrane domain and an intracellular Toll-IL-1 receptor

In the present study, we used microRNA (miRNA) sequencing to discover and explore the expression profiles of known and novel miRNAs in 1000 ng/ml LPS stimulated for 8 h vis-à-vis non-stimulated (i.e. control) PBMCs isolated from the blood of healthy pigs. A total of 291 known miRNAs were bio-computationally identified in porcine PBMCs, and 228 novel miRNAs (not enlisted in the swine mirBase) were identified

Immune cells encounter tissues with vastly different biochemical and physical characteristics. Much of the research emphasis has focused on the role of cytokines and chemokines in regulating immune cell function, but the role of the physical microenvironment has received considerably less attention. The tissue mechanics, or stiffness, of healthy tissues varies dramatically from soft adipose tissue

TLRs are a family of PRRs that respond to PAMPs or host-derived Danger-Associated Molecular Patterns (DAMPs) to initiate host inflammation and immune responses. TLR dimerization and recruitment of adapter molecules is critical for intracellular signaling and is mediated through intracellular Toll-Interleukin 1 Receptor Resistance (TIR) domain interactions. Human TIR domains, including reported structures

The ability to engineer pharmaceuticals that target the signal-dependent interactions of signaling proteins should revolutionize drug development. One approach to the rational design of protein interaction inhibitors uses decoy peptides, i.e. segments of protein primary sequence, which are derived from interfaces that mediate functional protein interactions. Decoy peptides often retain the ability

The review by Toshchakov and Javmen provides a comprehensive and authoritative perspective on the current state of development of cell-permeable peptide inhibitors of TLR signaling, the field to which the authors have become major contributors. The subject of this manuscript is important not only because of the importance of TLR in health and disease, but also because this approach might present a

This special issue of Innate Immunity is dedicated to Andrei E. Medvedev who passed away suddenly nearly a year ago. It was Andrei who conceived the idea of assembling a special issue of Innate Immunity that brought together articles written by individuals with a particular interest in the regulation of TLR biology. Andrei was known to all as a generous and able collaborator, as well as a rigorous