scholarly journals Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6683
Author(s):  
Markus M. Heimesaat ◽  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Stefan Bereswill
Keyword(s):  
Post Infection ◽  
Intestinal Tract ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Feed Additives ◽  
Gastrointestinal Pathogen ◽  
Obligate Anaerobic ◽  
Probiotic Treatment ◽  
Probiotic Product ◽  
First Time

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 805
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Systemic Circulation ◽  
Cell Responses ◽  
Pituitary Adenylate Cyclase ◽  
Gastrointestinal Colonization ◽  
First Time

Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

scholarly journals Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

2020 ◽  
Vol 8 (6) ◽  
pp. 802 ◽  
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Global Public Health ◽  
Food Borne ◽  
Human Infections ◽  
First Time ◽  
Post Infectious

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.

scholarly journals Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 818
Author(s):  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Stefan Bereswill ◽  
Markus Heimesaat
Keyword(s):  
Essential Oil ◽  
Infectious Diseases ◽  
Post Infection ◽  
Apoptotic Cell ◽  
Natural Compounds ◽  
Mesenteric Lymph Nodes ◽  
Beneficial Effects ◽  
Cell Responses ◽  
Food Borne ◽  
Human Campylobacteriosis

Human campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases.

scholarly journals The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

2020 ◽  
Vol 22 (1) ◽  
pp. 118
Author(s):  
Yuanpeng Zheng ◽  
Tessa A. Verhoeff ◽  
Paula Perez Pardo ◽  
Johan Garssen ◽  
Aletta D. Kraneveld
Keyword(s):  
Autism Spectrum Disorder ◽  
Intestinal Tract ◽  
Synapse Formation ◽  
Inflammatory Responses ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Protein Substrates ◽  
Specific Proteins ◽  
Membrane Bound

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intestines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, homeostasis and inflammation. These metalloproteases might be involved in microbiota-gut–brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut–brain axis.

Defects in the regulatory clearance mechanisms favor the breakdown of self-tolerance during spontaneous autoimmune orchitis

2009 ◽  
Vol 296 (3) ◽  
pp. R743-R762 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Suk Ran Yoon ◽  
Casimir D. Akpovi ◽  
Emil Silvas ◽  
María Leiza Vitale
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Plasma Membranes ◽  
Fas Ligand ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Self Tolerance ◽  
Tnf Α ◽  
Fas L ◽  
Autoimmune Orchitis

We identified aberrations leading to spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and natural model for autoimmunity. This study provides evidence favoring the view that a malfunction of the clearance mechanisms for apoptotic cell debris arising from imbalances in phagocyte receptors or cytokines acting on Sertoli cells constitutes a major factor leading to breakdown of self-tolerance during spontaneous AIO. Serum anti-sperm antibody titers measured by ELISA reflected spermatogenic activity without causing immune inflammatory responses. Orchitic mink showed excess antibody production accompanied by spermatogenic arrest, testicular leukocyte infiltration, and infertility. AIO serum labeled the postacrosomal region, the mid and end piece of mink sperm, whereas normal mink serum did not. Normal serum labeled plasma membranes, whereas AIO serum reacted with germ cell nuclei. Western blot analyses revealed that AIO serum reacted specifically to a 23- and 50-kDa protein. The number of apostain-labeled apoptotic cells was significantly higher in orchitic compared with normal tubules. However, apoptosis levels measured by ELISA in seminiferous tubular fractions (STf) were not significantly different in normal and orchitic tubules. The levels of CD36, TNF-α, TNF-α RI, IL-6, and Fas but not Fas-ligand (L), and ATP-binding cassette transporter ABCA1 were changed in AIO STf. TNF-α and IL-6 serum levels were increased during AIO. Fas localized to germ cells, Sertoli cells, and the lamina propria of the tubules and Fas-L, to germ cells. Fas colocalized with Fas-L in residual bodies in normal testis and in giant cells and infiltrating leukocytes in orchitic tubules.

scholarly journals EnteroaggregativeEscherichia coliAdherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Erik J. Boll ◽  
Jorge Ayala-Lujan ◽  
Rose L. Szabady ◽  
Christopher Louissaint ◽  
Rachel Z. Smith ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Cell Receptor ◽  
Host Cell Receptor ◽  
Intestinal Infections ◽  
Elevated Expression ◽  
Intestinal Pathogen ◽  
Proinflammatory Role ◽  
First Time

ABSTRACTEnteroaggregativeEscherichia coli(EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen.IMPORTANCEEAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.

scholarly journals Overexposure to apoptosis via disrupted glial specification perturbs Drosophila macrophage function and reveals roles of the CNS during injury

2020 ◽  
Author(s):  
Emma Louise Armitage ◽  
Hannah Grace Roddie ◽  
Iwan Robert Evans
Keyword(s):  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Calcium Waves ◽  
Apoptotic Cells ◽  
Phagocytic Cells ◽  
Macrophage Function ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance ◽  
Wound Responses

AbstractApoptotic cell clearance by phagocytes is a fundamental process during development, homeostasis and the resolution of inflammation. However, the demands placed on phagocytic cells such as macrophages by this process, and the limitations these interactions impose on subsequent cellular behaviours are not yet clear. Here we seek to understand how apoptotic cells affect macrophage function in the context of a genetically-tractable Drosophila model in which macrophages encounter excessive amounts of apoptotic cells. We show that loss of the glial transcription factor repo, and corresponding removal of the contribution these cells make to apoptotic cell clearance, causes macrophages in the developing embryo to be challenged with large numbers of apoptotic cells. As a consequence, macrophages become highly vacuolated with cleared apoptotic cells and their developmental dispersal and migration is perturbed. We also show that the requirement to deal with excess apoptosis caused by a loss of repo function leads to impaired inflammatory responses to injury. However, in contrast to migratory phenotypes, defects in wound responses cannot be rescued by preventing apoptosis from occurring within a repo mutant background. In investigating the underlying cause of these impaired inflammatory responses, we demonstrate that wound-induced calcium waves propagate into surrounding tissues, including neurons and glia of the ventral nerve cord, which exhibit striking calcium waves on wounding, revealing a previously unanticipated contribution of these cells during responses to injury. Taken together these results demonstrate important insights into macrophage biology and how repo mutants can be used to study macrophage-apoptotic cell interactions in the fly embryo.Furthermore, this work shows how these multipurpose cells can be ‘overtasked’ to the detriment of their other functions, alongside providing new insights into which cells govern macrophage responses to injury in vivo.

scholarly journals Experimental infection of sheep with visna/maedi virus via the conjunctival space

2008 ◽  
Vol 89 (6) ◽  
pp. 1329-1337 ◽  
Author(s):  
Heide Niesalla ◽  
Tom N. McNeilly ◽  
Margaret Ross ◽  
Susan M. Rhind ◽  
Gordon D. Harkiss
Keyword(s):  
Post Infection ◽  
Mononuclear Cells ◽  
Mediastinal Lymph Node ◽  
Ocular Tissue ◽  
Ocular Infection ◽  
Peripheral Blood Mononuclear ◽  
Ocular Tissues ◽  
Virus Dose ◽  
Low Levels ◽  
First Time

Experiments were performed to determine whether visna/maedi virus (VMV), a small ruminant lentivirus (SRLV), could infect sheep via ocular tissues. The EV1 strain of VMV was administered into the conjunctival space of uninfected sheep, and the animals monitored for the presence of provirus DNA and anti-VMV antibodies in blood. The results showed that provirus DNA appeared in peripheral blood mononuclear cells of all animals within a few weeks of receiving either 106 TCID50 or 103 TCID50 of VMV. Of the animals receiving the higher dose of virus via the conjunctival space, two seroconverted by 7 and 10 weeks post-infection, one seroconverted 8 months post-infection, and one had not seroconverted by 15 months post-infection. With the lower virus dose, the animals infected via the trachea seroconverted by 4 and 14 weeks, respectively. After ocular infection with this dose, one animal showed a transitory seroconversion with low levels of antibody, peaking at 2 weeks post-administration. The remaining three of the animals infected via the eyes did not seroconvert over a period of 13 months. At post-mortem, evidence for the presence of proviral DNA was obtained from ocular tissue, lungs or mediastinal lymph node in both groups of animals. Histological analysis of lung tissue from animals receiving the lower dose of virus showed the presence of early inflammatory lesions. The results thus show for the first time that transmission of VMV can occur via ocular tissues, suggesting that the conjunctival space may be an additional route of natural transmission.

scholarly journals Polystyrene microplastics induce an immunometabolic active state in macrophages

2021 ◽  
Author(s):  
Seth Merkley ◽  
Harrison C Moss ◽  
Samuel M Goodfellow ◽  
Christina L Ling ◽  
Jewel L Meyer-Hagen ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Inflammatory Responses ◽  
Metabolic Response ◽  
Environmental Pollutants ◽  
Cytokine Gene Expression ◽  
Cell Surface Markers ◽  
Cytokine Gene ◽  
Plastic Pollution ◽  
First Line ◽  
Metabolic Switch

Abstract Anti- and pro-inflammatory responses in macrophages are influenced by cellular metabolism. Macrophages are the primary phagocyte in mucosal environments (i.e., intestinal tract and lungs) acting as first-line defense against microorganisms and environmental pollutants. Given we now face extensive microplastic contamination of our food and water sources, we aimed to examine the metabolic response in macrophages to microplastic particles (MP). Utilizing murine macrophages, we assessed the metabolic response of macrophages after polystyrene MP phagocytosis. The phagocytosis of MP by macrophages induced a metabolic shift toward glycolysis and a reduction in mitochondrial respiration that was associated with an increase of cell surface markers CD80 and CD86 and cytokine gene expression associated with glycolysis. The gastrointestinal consequences of this metabolic switch in the context of an immune response remains uncertain but the global rise of plastic pollution and MP ingestion potentially pose an unappreciated health risk.

Attenuation of apoptosis in enterocytes by blockade of potassium channels

2005 ◽  
Vol 289 (5) ◽  
pp. G815-G821 ◽  
Author(s):  
Anatoly Grishin ◽  
Henri Ford ◽  
Jin Wang ◽  
Hui Li ◽  
Vicenta Salvador-Recatala ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Cell Loss ◽  
Cell Types ◽  
Epithelial Cell Line ◽  
Channel Blockers ◽  
Pharmacological Prevention ◽  
Pharmacological Blockade ◽  
Inflammatory Bowel ◽  
First Time

Apoptosis plays an important role in maintaining the balance between proliferation and cell loss in the intestinal epithelium. Apoptosis rates may increase in intestinal pathologies such as inflammatory bowel disease and necrotizing enterocolitis, suggesting pharmacological prevention of apoptosis as a therapy for these conditions. Here, we explore the feasibility of this approach using the rat epithelial cell line IEC-6 as a model. On the basis of the known role of K+ efflux in apoptosis in various cell types, we hypothesized that K+ efflux is essential for apoptosis in enterocytes and that pharmacological blockade of this efflux would inhibit apoptosis. By probing intracellular [K+] with the K+-sensitive fluorescent dye and measuring the efflux of 86Rb+, we found that apoptosis-inducing treatment with the proteasome inhibitor MG-132 leads to a twofold increase in K+ efflux from IEC-6 cells. Blockade of K+ efflux with tetraethylammonium, 4-aminopyridine, stromatoxin, chromanol 293B, and the recently described K+ channel inhibitor 48F10 prevents DNA fragmentation, caspase activation, release of cytochrome c from mitochondria, and loss of mitochondrial membrane potential. Thus K+ efflux occurs early in the apoptotic program and is required for the execution of later events. Apoptotic K+ efflux critically depends on activation of p38 MAPK. These results demonstrate for the first time the requirement of K+ channel-mediated K+ efflux for progression of apoptosis in enterocytes and suggest the use of K+ channel blockers to prevent apoptotic cell loss occurring in intestinal pathologies.

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