TLR signalling

Neuronal dysfunction initiates several intracellular signaling cascades to release different proinflammatory cytokines and chemokines, as well as various reactive oxygen species. In addition to neurons, microglia, and astrocytes are also affected by this signaling cascade. This release can either be helpful, neutral or detrimental for cell survival. Toll-like receptors (TLRs) activate and signal their downstream pathway to activate NF-κB and pro-IL-1β, both of which are responsible for neuroinflammation and linked to the pathogenesis of different age-related neurological conditions. However, herein, recent aspects of polyphenols in the treatment of neurodegenerative diseases are assessed, with a focus on TLR regulation by polyphenols. Different polyphenol classes, including flavonoids, phenolic acids, phenolic alcohols, stilbenes, and lignans can potentially target TLR signaling in a distinct pathway. Further, some polyphenols can suppress overexpression of inflammatory mediators through TLR4/NF-κB/STAT signaling intervention, while others can reduce neuronal apoptosis via modulating the TLR4/MyD88/NF-κB-pathway in microglia/macrophages. Indeed, neurodegeneration etiology is complex and yet to be completely understood, it may be that targeting TLRs could reveal a number of molecular and pharmacological aspects related to neurodegenerative diseases. Thus, activating TLR signaling modulation via natural resources could provide new therapeutic potentiality in the treatment of neurodegeneration.

Toll-like receptors (TLRs) are evolutionarily conserved innate immune receptors that recognize
pathogen specific molecular pattern (PAMPs) in an efficient, non-self-reactive manner
and initiate specific immune signaling that culminates in triggering antigen-specific adaptive
responses. Different TLR genes in domestic animal species have been characterized and
accumulating evidence from recent studies indicates an extended role for TLR signaling in
reproductive physiology. In females, TLRs have been implicated in the regulation of ovulation,
fertilization, gestation and parturition, as well as in pathological conditions such as
endometritis and mastitis. In males, TLRs play a role in steroidogenesis and spermatogenesis.
Use of TLR agonists has also been shown to be effective in the treatment of certain
reproductive tract infections. Moreover, gene polymorphisms in TLRs have been associated
with mastitis providing evidence that TLRs can potentially be exploited as markers in future
breeding programs. The aim of this review is to provide a comprehensive treatise on role
of TLRs in male and female reproductive physiology and associated pathology in domestic
livestock.

Toll-like Receptors (TLRs), the evolutionarily conserved molecules are identified as the pattern recognition receptors (PRRs) in vertebrates and invertebrates which recognize the pathogen-associated molecular patterns (PAMPs). The TLRs signaling is via interactions with adaptor proteins including MyD88 and toll receptor associated activator of interferon (TRIF). They directly detect the pathogen invasion and induce either immuno-stimulatory or immunomodulatory biological response. This ability of TLRs to modulate the immune system has been taken in concern in recent studies to develop an adaptive immunotherapy against cancer and several other neurological disorders. Moreover, to trace their auxiliary therapeutic effects, the TLR agonists are now undergoing the extensive clinical investigation. This review discusses the therapeutic potential of TLRs as Immunostimulators and Immunomodulators. Alongside, the association of TLRs with autoimmune responses and human diseases is also explored.
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Introduction: In this study we focused on novel antischistosomal toll-like receptor (TLR) agonists which induced immune cells to produce a plethora of inflammatory cytokines against shistosoma mansoni infection. We used in this study two importants agonists TLR3L (polyinosinicsalsidylic acid; poly I:C) andTLR2L zymosan. We divided this study into 2 experiments 1. The adjuvant effect of polyI:C orzymosan with soluble worm antigen (SWAP antigen) and we divided it into negative control group, positive control group,vaccinated group with SWAP antigen, vaccinated group with SWAP antigen plus poly I:C,vaccinated group with SWAP antigen pluszymosan 2. Antischistosomal effect of poly I:C orzymosan and we divided it intonegative control group, two positive control groups, treated groups with poly(I:C) on day 25 or day 35 after infection, treated groups with zymosan on day 25 and day 35 after infection. Antischistosomal effect of poly I:C or zymosan was evaluated by measuring serum biochemical parameters as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, albumin and total protein. We measured also oxidative stress parameters such as glutathione S. transferase, catalase, total antioxidant capacity, total thiol and malondialdehyde in liver homogenate, in addition to the histopathological examinations of all mice liver tissue with measuring granuloma sizes of all infected and treated groups and finally we measured the parasitological parameters as worm burden, liver and intestine eggs count.

Background: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy. Discussion: So far, several studies have proposed different targets such as cyclooxygenase-2 (COX-2), some toll-like receptors (TLRs), mitogen-activated protein kinases (MAPKs) etc., for the amelioration of radiation toxicity and enhancing tumor response. NADPH oxidase includes five NOX and two dual oxidases (DUOX1 and DUOX2) subfamilies that through the production of superoxide and hydrogen peroxide, play key roles in oxidative stress and several signaling pathways involved in early and late effects of ionizing radiation. Chronic ROS production by NOX enzymes can induce genomic instability, thereby increasing the risk of carcinogenesis. Also, these enzymes are able to induce cell death, especially through apoptosis and senescence that may affect tissue function. ROS-derived NADPH oxidase causes apoptosis in some organs such as intestine and tongue, which mediate inflammation. Furthermore, continuous ROS production stimulates fibrosis via stimulation of fibroblast differentiation and collagen deposition. Evidences have shown that in contrast to normal tissues, the NOX system induces tumor resistance to radiotherapy through some mechanisms such as induction of hypoxia, stimulation of proliferation, and activation of macrophages. However, there are some contradictory results. Inhibition of NADPH oxidase in experimental studies has shown promising results for both normal tissue protection and tumor sensitization to ionizing radiation. Conclusion: In this article, we aimed to review the role of different subfamilies of NADPH oxidase in radiation-induced early and late normal tissue toxicities in different organs.

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at  least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked
TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202  male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None
of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years)  tested carry such TLR7 variants (p = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases
infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from
a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a
deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general
population is < 6.5x10−4. We also show that blood B cell lines and myeloid cell subsets from the patients do
not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid
dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked
recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about
1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I
IFN immunity against SARS-CoV-2 in the respiratory trac

responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect. Conclusions: This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

Toll-like receptors (TLRs) are a group of highly conserved molecules that initiate
innate immune responses to pathogens by recognizing structural motifs. In response
to pathogen associated molecular patterns (PAMPs), TLRs induce the production of
reactive oxygen and nitrogen intermediates (ROI and RNI), inflammatory cytokines
and up regulate the expression of co-stimulatory molecules, subsequently initiating
adaptive immunity. Ten chicken TLR genes have been identified and their
association with various diseases has been ascertained. This review concerns
chicken toll-like receptors, their structure, expression, signalling, and their role in
innate and adaptive immunity and disease resistance. It is concluded that TLR genes
could be used as molecular markers for genetic selection for the improvement of
disease resistance and TLR agonists as potential adjuvants in future vaccines.

Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected. Thus, using standardized vectors and reporter assays, we characterized activities by each IFN antagonist from all known ebolavirus and marburgvirus species side-by-side. We uncover noncanonical suppression of IFN induction by ebolavirus VP24, differing potencies by MARV and RAVV proteins, and intriguingly, weaker antagonism by VP24 of RESTV. These underlying molecular explanations for differential virulence in humans could guide future investigations of more-neglected filoviruses as well as treatment and vaccine studies.

Chagas Heart disease is caused by the infection with T. cruzi. The mechanisms of disease progression remain largely unknown although it has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants for the clinical manifestations of the disease.
Through a long co-evolutionary history, both the human immune system and the pathogen have acquired diverse mechanisms to interact, guaranteeing their mutual survival. Even though inflammation is indispensable for host defense and tissue repair, when deregulated or disproportionate, it can contribute to continuous tissue injury, organ dysfunction, and disease. Thus, the immune system has acquired a great complexity in order to maintain the host’s integrity while it is able to arrest the proliferation of pathogens as soon as detected.
This chapter aims to review the regulatory mechanisms involved in the control of the effectors mechanisms of the innate immunity during experimental T. cruzi infection and Chagas disease. It provides a comprehensive revision of the immunologic mechanisms triggered by the interaction of the parasite and the host cells during acute phase of the infection, as well as the possible implications for the design of therapeutic or diagnostic approaches.

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele f...

Preventive vaccination is the most successful approach against infectious diseases and has a great impact on world health. Vaccines operate through the activation of innate immunity that helps to stimulate antigen-specific T- and B-lymphocytes. These events are orchestrated by dendritic cells (DCs) that are able to sample foreign structures and concomitantly sense ‘danger signals’. Thus, DCs provide a functional link between innate and acquired immunity, and due to their regulatory potential are referred to as natural adjuvants. Human conventional and plasmacytoid DCs express different sets of well-characterized Toll-like membrane receptors (TLRs) that recognize a broad range of conserved molecular patterns of pathogens. The recently discovered cytosolic Nod-like receptors (NLRs) and RIG-like helicases (RLHs) also turned out to participate in pathogen recognition and modulation of immune responses through interacting signaling pathways. As a result of their collaboration, the TLR, N...

Oligodeoxynucleotides (ODNs) containing cytosine-phosphate-guanosine sequence (CpG) is considered as an immune stimulator when it is fed to animals. These synthetic molecules mount different immune responses in the animals including mice, chickens, ducks, dogs and horses. CpG ODNs induce specific antigenic immunity against co-administered vaccines and are well tolerated in healthy individuals and are capable of stimulating toll-like receptors (TLRs) such as TLR-9 to activate innate immunity. The CpG ODNs can be used as an adjuvant in different vaccines synthesised specifically for poultry diseases caused by viruses and bacteria. In chickens, CpG ODNs stimulate TLRs involved in humoral immunity. CpG ODNs have been used as mucosal vaccine adjuvants against several pathogens, including avian influenza and Newcastle disease. The CpG ODNs function to protect the chickens from Newcastle disease by producing plasma dendric cells (pDCs) which ultimately produce interferons (INFs). The inoculation of CpG ODNs along with the cationic microparticles and DNA vaccine for infectious bursal disease virus result in the influx of T cells and a reduction of antigen load. When CpG ODNs are used against avian leucosis, they result in significantly higher antibody titres. In many other vaccines e.g., infectious laryngotracheitis, infectious bronchitis, herpes, viral enteritis, Marek's disease virus, E. coli and Salmonella spp. including CpG ODNs exhibit immunostimulatory effects. In conclusion, CpG ODNs may be used as effective adjuvants in viral, bacterial and parasitic vaccines in poultry.

Redox regulation depends on the enzymatically controlled production and decay of redox active molecules. NADPH oxidases, superoxide dismutases, nitric oxide synthases, and others produce the redox active molecules superoxide, hydrogen peroxide, nitric oxide, and hydrogen sulfide. These react with target proteins inducing spatiotemporal modifications of cysteine residues within different signaling cascades. Thioredoxin family proteins are key regulators of the redox state of proteins. They regulate the formation and removal of oxidative modifications by specific thiol reduction and oxidation. All of these redox enzymes affect inflammatory processes and the innate and adaptive immune response. Interestingly, this regulation involves different mechanisms in different biological compartments and specialized cell types. The localization and activity of distinct proteins including, for instance, the transcription factor NFκB and the immune mediator HMGB1 are redox-regulated. The transmembrane protein ADAM17 releases proinflammatory mediators, such as TNFα, and is itself regulated by a thiol switch. Moreover, extracellular redox enzymes were shown to modulate the activity and migration behavior of various types of immune cells by acting as cytokines and/or chemokines. Within this review article, we will address the concept of redox signaling and the functions of both redox enzymes and redox active molecules in innate and adaptive immune responses.

The innate immune system recognises a wide spectrum of pathogens without a need for prior exposure. The main cells responsible aremonocytes, macrophages, dendritic cells (DC) and neutrophils phagocytose microbial pathogens triggering a cytokine network resulting inthe development of inflammatory and specific immune responses. Findings in the Toll-like receptor (TLR) family, initially discovered inDrosophila, further elucidated these processes. Toll-like receptors induce activation of an innate immune response and at present ten TLRshave been identified, named TLRs 1–10. In addition to the ignition of the innate immune response, evidence implicates the TLR family ina spectrum of systemic disorders following bacterial infections including sepsis and multiple organ failure, and can be detrimental, leadingto tissue injury. In this project, our main goal was to investigate the effects of a TLR4 ligand, lipolysaccharide (LPS) in human DC andmonocytes. Our hypothesis is that different professional APCs, express different mRNA TLR transcripts. Our findings indicate that TLRexpression patterns change in relation to the pathogen involved and in the case of DC, and the maturation stage the latter are upon challenging.Our results and interpretation showed significant alteration of transcript expression patterns upon LPS challenge in all cell subsets, with DCsubsets expressing different TLR mRNA patterns as they go through different maturation stages.

Endotoxin (LPS)-induced changes in histone lysine methylation contribute to the gene-specific transcription for control of inflammation. Still unidentified are the chromatin regulators that drive the transition from a transcriptional-repressive to a transcriptional-active chromatin state of pro-inflammatory genes. Here, using combined approaches to analyze LPS-induced changes in both gene-specific transcription and protein secretion to the extracellular compartment, we characterize novel functions of the lysine demethylase PHF8 as a pro-inflammatory, gene-specific chromatin regulator. First, in the LPS-induced, acute-inflamed macrophages, PHF8 knockdown led to both a reduction of pro-inflammatory factors and an increase in a transcriptional-repressive code (H3K9me2) written by the methyltransferase G9a. Through unbiased quantitative secretome screening we discovered that LPS induces the secretion of a cluster of PHF8-dependent, 'tolerizable' proteins that are related to diverse extracellular pathways/processes including those for the activation of adaptive immunity. Specifically, we determined that PHF8 promotes T-cell activation and proliferation, thus providing the first link between the epigenetic regulation of inflammation and adaptive immunity. Further, we found that, in the acute-inflamed macrophages, the acute-active PHF8 opposes the H3K9me1/2-writing activity of G9a to activate specific protein secretions that are suppressed by G9a in the endotoxin-tolerant cells, revealing the inflammatory-phenotypic chromatin drivers that regulate the gene-specific chromatin plasticity. Activation of inflammation, the key host innate immune response to microbial challenge 1 , is a double-edged sword; it protects the host from infection and cellular damage, yet, its deregulation contributes directly to various inflammation-associated pathologies 2,3. Previous studies indicated that control of inflammation is achieved by endotoxin-or lipopolysaccharide (LPS)-induced gene-specific chromatin modifications. The landscape of promoter chromatin modifications is differentially programmed for a class of pro-inflammatory or " tolerizeable " (T-class) genes, in correlation with either acutely or chronically inflamed nature or " inflammatory-phenotype " of the stimulated cells 4. However, how inflammation-phenotypic plasticity is regulated within the chromatin of pro-inflammatory genes is poorly understood. The properties of histones, the core components of chromatin, can be altered by different post-translational modifications (PTMs) that specify whether the promoter of associated gene is in an open/active or closed/

The nuclear interferon-inducible-16 (IFI16) protein acts as DNA sensor in inflammasome signaling and as viral restriction factor. Following Herpesvirus infection or UV-B treatment, IFI16 delocalizes from the nucleus to the cytoplasm and is eventually released into the extracellular milieu. Recently, our group has demonstrated the occurrence of IFI16 in sera of systemic-autoimmune patients that hampers biological activity of endothelia through high-affinity membrane binding. As a continuation, we studied the activity of endotoxin-free recombinant IFI16 (rIFI16) protein on primary endothelial cells. rIFI16 caused dose/time-dependent upregulation of IL-6, IL-8, CCL2, CCL5, CCL20, ICAM1, VCAM1, and TLR4, while secretion of IL-6 and IL-8 was amplified with lipopolysaccharide synergy. Overall, cytokine secretion was completely inhibited in MyD88-silenced cells and partially by TLR4-neutralizing antibodies. By screening downstream signaling pathways, we found that IFI16 activates p38, p44/...

The three-way need for higher data rates, good quality of service and ubiquity in a converged all IP communication cloud drives research in wireless communication. Wireless access networks are envisaged candidates of the next generation wireless networks. The various access networks will be integrated with other technologies including the wired backbone. The major issues in an all IP and converged networks are: quality of service, seamless handover and network capacity. Emerging research seeks to address these
open research issues; for example the implementation of multi-channel and multi radio MAC protocols in WMN. In this paper we analyze and evaluate the effectiveness of multi-channel and multi radio techniques in WMN. The shortcomings of these schemes are highlighted and possible solutions are suggested. The signalling delay metric is used for evaluation purposes. The focus is on the performance of the control channel identified as the critical performance metric of multi-channel MAC protocols

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele f...

Metainflammation and malfunctions of toll-like receptor 4 (TLR4) are related to obesity-induced immunometabolic morbidities. There are almost no studies relating exercise training to the TLR4 pathway and its adaptors and negative regulators. Thirty young women with obesity (exercise group and control group) were included in a 10-week all-extremity combined high-intensity interval training program. The immunomodulatory impacts of exercise on TLR4, its related adaptors (TIR domain-containing adaptor-inducing IFN-β [TRIF], myeloid differentiation factor 88 [MyD88], and tumor receptor-associated factor 6 [TRAF6]), transcriptional factors (nuclear factor [NF]-κB and interferon regulatory factor 3 [IRF3]), and negative regulator (A20) mRNA levels were assessed by real-time PCR. Also, the serum concentration of TLR4 final products (tumor necrosis factor α [TNFα] and interferon γ [IFNγ]) was measured by ELISA. Cardiorespiratory and body composition parameters were tested, as well. There was a significant improvement in body composition and cardiorespiratory fitness. This intervention downregulated TLR4 (from 2.25 ± 1.07 to 0.84 ± 1.01), MyD88 (from 4.53 ± 5.15 to 1.27 ± 0.88), NF-κB (from 1.61 ± 2.03 to 0.23 ± 0.39), IRF3 (from 1.22 ± 0.77 to 0.25 ± 0.36), and A20 (from 0.88 ± 0.59 to 0.22 ± 0.33) levels and reduced the TNFα concentrations (from 22.39 ± 11.43 to

Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR stimulated eosinophils were inoculated i.p. into wildtype mice, NK cells were rapidly recruited and exhibited anti-tumor cytotoxicity. However when mice depleted of CD11c+ cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG stimulated eosinophils respectively, NK cell recruitment was still observed alongside cytotoxicity and IFNγ production. CpG-stimulation of eosinophils produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are important for NK cell activation and recruitment in vivo. To demonstrate the importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated eosinophils pre-treated with the gut microbial metabolite butyrate had reduced expression and production of CXCL10 and IL-12 and concomitantly were poor at recruitment of NK cells and inducing IFNγ in NK cells. Therefore, eosinophils like other innate immune cells of myeloid origin can conceivably stimulate NK cell activity. In addition, products of the gut microbiota can be potential inhibitors of NK cell activation and recruitment by dampening pro-inflammatory cytokines.

Listeria monocytogenes is a Gram-positive bacterium that can cause a serious infection. Intestinal microorganisms have been demonstrated to contribute to intestinal physiology not only through immunological responses but also by modulating the intestinal serotonergic system. Serotonin (5-HT) is a neuromodulator that is synthesized in the intestinal epithelium and regulates the whole intestinal physiology. The serotonin transporter (SERT), located in enterocytes, controls intestinal 5-HT availability and therefore serotonin's effects. Infections caused by L. monocytogenes are well described as being due to the invasion of intestinal epithelial cells; however , the effect of L. monocytogenes on the intestinal epithelium remains unknown. The main aim of this work, therefore, was to study the effect of L. monocytogenes on SERT. Caco2/TC7 cell line was used as an enterocyte-like in vitro model, and SERT functional and molecular expression assays were performed. Our results demonstrate that living L. monocytogenes inhibits serotonin uptake by reducing SERT expression at the brush border membrane. However, neither inactivated L. monocytogenes nor soluble metabolites were able to affect SERT. The results also demonstrate that L. monocytogenes yields TLR2 and TLR10 transcriptional changes in intestinal epithelial cells and suggest that TLR10 is potentially involved in the inhibitory effect observed on SERT. Therefore, L. monocytogenes, through TLR10-mediated SERT inhibition , may induce increased intestinal serotonin availability and potentially contributing to intestinal physiological changes and the initiation of the inflammatory response.