scholarly journals Selenium Status Alters the Immune Response and Expulsion of Adult Heligmosomoides bakeri Worms in Mice

2013 ◽  
Vol 81 (7) ◽  
pp. 2546-2553 ◽  
Author(s):  
Allen D. Smith ◽  
Lumei Cheung ◽  
Ethiopia Beshah ◽  
Terez Shea-Donohue ◽  
Joseph F. Urban
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Metabolic Activity ◽  
Surrounding Tissue ◽  
Th2 Response ◽  
Content Type ◽  
Adequate Diet ◽  
Th2 Immune Response ◽  
Heligmosomoides Bakeri ◽  
Deficient Mice

ABSTRACTHeligmosomoides bakeriis a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adultH. bakeriworms from a challenge infection was delayed in selenium (Se)-deficient mice. In order to explore mechanisms associated with the delayed expulsion, 3-week-old female BALB/c mice were placed on a torula yeast-based diet with or without 0.2 ppm Se, and after 5 weeks, they were inoculated withH. bakeriinfective third-stage larvae (L3s). Two weeks after inoculation, the mice were treated with an anthelmintic and then rested, reinoculated with L3s, and evaluated at various times after reinoculation. Analysis of gene expression in parasite-induced cysts and surrounding tissue isolated from the intestine of infected mice showed that the local-tissue Th2 response was decreased in Se-deficient mice compared to that in Se-adequate mice. In addition, adult worms recovered from Se-deficient mice had higher ATP levels than worms from Se-adequate mice, indicating greater metabolic activity in the face of a suboptimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within 2 to 4 days after feeding a Se-adequate diet to Se-deficient mice. Expulsion was associated with an increased local expression of Th2-associated genes in the small intestine, intestinal glutathione peroxidase activity, secreted Relm-β protein, anti-H. bakeriIgG1 production, and reduced worm fecundity and ATP-dependent metabolic activity.

scholarly journals A10 FOOD ANTIGEN-STRESS INTERACTION LEADS TO INCREASE PAIN SIGNALING IN ILEUM AND COLON VIA STAT6 IN AN IBS MODEL

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 11-12
Author(s):  
C Lopez Lopez ◽  
J Jaramillo Polanco ◽  
Y Yu ◽  
Q K Tsang ◽  
S Vanner ◽  
...  
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Afferent Nerve ◽  
Drg Neurons ◽  
Drg Neuron ◽  
Food Antigen ◽  
Neuron Excitability ◽  
Th2 Immune Response ◽  
Antigen Interaction ◽  
Deficient Mice

Abstract Background Abdominal pain can be triggered by food ingestion in IBS patients. Previously we have shown that a food antigen induces local release of immune mediators in the colon that increase dorsal root ganglion (DRG) neuron excitability when there is previous antigen exposure in the presence of psychological stress. However, it is unknown if this effect is limited to the colon. Furthermore, the involvement of histamine in the neuronal hyperexcitability suggests that the stress-food antigen interaction evokes a Th2 immune response. Thus, we sought to investigate the role of STAT6, a transcription factor downstream of Th2 cytokines and important for IgE production. Aims 1) Determine if stress-food antigen interaction leads to release of mediators within the small intestine that increase DRG neuron excitability. 2) Determine the involvement of STAT6 on neuronal hyperexcitability induced by the stress-food antigen interaction. Methods BALB/c mice were exposed to water avoidance stress (WAS) or sham stress (SHAM) for 1 hr daily for 10 days. On day 2–10, mice were exposed to ovalbumin (OVA) or saline (SAL). Seven days later, mice were re-exposed to either OVA or SAL every 2 days for 2 weeks yielding 3 groups: WAS/OVA+OVA, WAS/SAL+OVA, and SHAM/OVA+OVA. STAT6 deficient mice were also exposed to WAS/OVA+OVA protocol. Ileum or colonic supernatants were obtained 4 hours after tissue collection. DRG neurons were incubated overnight with supernatants prior to perforated patch clamp recordings. Neuronal excitability was evaluated by measuring the rheobase (minimum current to elicit an action potential, decreased rheobase indicates increased excitability). Mechanosensitivity of extrinsic afferent nerves innervating distal ileum was examined using ex vivo extracellular afferent nerve recordings. Data was analyzed by one or two-way ANOVA with Bonferroni post-hoc test. Results Ileum supernatants from WAS/OVA+OVA mice increased DRG neuron excitability compared to WAS/SAL+OVA and SHAM/OVA+OVA mice (63.3 ± 6.2 pA vs 83.2 ± 5.4 pA, 86.7 ± 4.5 pA, p<0.05). Ileum afferent nerve response to distention was significantly augmented in WAS/OVA+OVA mice compared to WAS/SAL+OVA and SHAM/OVA+OVA (P<0.05, n=4–7). DRG neurons incubated with WAS/OVA+OVA supernatant from STAT6 deficient mice were less excitable compared to neurons incubated with colonic supernatants from wild type mice (86.5 ± 4.1 pA vs 67.6 ± 4.8 pA, p<0.05). Conclusions Stress-food antigen interaction releases mediators in both the small intestine and colon to increase nociceptive signaling, an important finding as IBS can involve both areas. The release of excitatory mediators within the gut appears to involve STAT6. Thus, a stress-food antigen interaction evoking a Th2 immune response in the gut may be a mechanism underlying food induced symptoms in IBS. Funding Agencies Queen’s University, Department of Medicine

scholarly journals A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X duringAcinetobacter baumanniiInfection

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Jacob E. Choby ◽  
Andrew J. Monteith ◽  
Lauren E. Himmel ◽  
Paris Margaritis ◽  
Jana K. Shirey-Rice ◽  
...  
Keyword(s):  
Immune Response ◽  
Association Study ◽  
Immune Cell ◽  
Coagulation Factor ◽  
Factor X ◽  
Human Pathogens ◽  
Chemokine Production ◽  
Content Type ◽  
Factor X Deficiency ◽  
Deficient Mice

ABSTRACTCoagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protected from systemicAcinetobacter baumanniiinfection, suggesting that factor X plays a role in the immune response toA. baumannii. Factor X deficiency was associated with reduced cytokine and chemokine production and alterations in immune cell population during infection: factor X-deficient mice demonstrated increased abundance of neutrophils, macrophages, and effector T cells. Together, these results suggest that factor X activity is associated with an inefficient immune response and contributes to the pathology ofA. baumanniiinfection.

scholarly journals Vibrio cholerae at the Intersection of Immunity and the Microbiome

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ana A. Weil ◽  
Rachel L. Becker ◽  
Jason B. Harris
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Immune Responses ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Intestinal Microbiome ◽  
Secretory Diarrhea ◽  
Content Type ◽  
New Approaches

ABSTRACT Vibrio cholerae is a noninvasive pathogen that colonizes the small intestine and produces cholera toxin, causing severe secretory diarrhea. Cholera results in long lasting immunity, and recent studies have improved our understanding of the antigenic repertoire of V. cholerae. Interactions between the host, V. cholerae, and the intestinal microbiome are now recognized as factors which impact susceptibility to cholera and the ability to mount a successful immune response to vaccination. Here, we review recent data and corresponding models to describe immune responses to V. cholerae infection and explain how the host microbiome may impact the pathogenesis of V. cholerae. In the ongoing battle against cholera, the intestinal microbiome represents a frontier for new approaches to intervention and prevention.

scholarly journals Impact of Mosquito Bites on Asexual Parasite Density and Gametocyte Prevalence in Asymptomatic Chronic Plasmodium falciparum Infections and Correlation with IgE and IgG Titers

2012 ◽  
Vol 80 (6) ◽  
pp. 2240-2246 ◽  
Author(s):  
Ramatoulaye Lawaly ◽  
Lassana Konate ◽  
Laurence Marrama ◽  
Ibrahima Dia ◽  
Diawo Diallo ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Salivary Gland ◽  
Parasite Density ◽  
Parasite Prevalence ◽  
Asexual Parasite ◽  
Salivary Gland Extract ◽  
Th2 Response ◽  
Content Type ◽  
Asymptomatic Infections

ABSTRACTAn immunomodulatory role of arthropod saliva has been well documented, but evidence for an effect onPlasmodiumsp. infectiousness remains controversial. Mosquito saliva may orient the immune response toward a Th2 profile, thereby priming a Th2 response against subsequent antigens, includingPlasmodium. Orientation toward a Th1 versus a Th2 profile promotes IgG and IgE proliferation, respectively, where the former is crucial for the development of an efficient antiparasite immune response. Here we assessed the direct effect of mosquito bites on the density ofPlasmodium falciparumasexual parasites and the prevalence of gametocytes in chronic, asymptomatic infections in a longitudinal cohort study of seasonal transmission. We additionally correlated these parasitological measures with IgE and IgG antiparasite and anti-salivary gland extract titers. The mosquito biting density was positively correlated with the asexual parasite density but not asexual parasite prevalence and was negatively correlated with gametocyte prevalence. Individual anti-salivary gland IgE titers were also negatively correlated with gametocyte carriage and were strongly positively correlated with antiparasite IgE titers, consistent with the hypothesis that mosquito bites predispose individuals to develop an IgE antiparasite response. We provide evidence that mosquito bites have an impact on asymptomatic infections and differentially so for the production of asexual and sexual parasites. An increased research focus on the immunological impact of mosquito bites during asymptomatic infections is warranted, to establish whether strategies targeting the immune response to saliva can reduce the duration of infection and the onward transmission of the parasite.

scholarly journals Periostin and Thymic Stromal Lymphopoietin—Potential Crosstalk in Obstructive Airway Diseases

2020 ◽  
Vol 9 (11) ◽  
pp. 3667
Author(s):  
Patrycja Nejman-Gryz ◽  
Katarzyna Górska ◽  
Magdalena Paplińska-Goryca ◽  
Małgorzata Proboszcz ◽  
Rafał Krenke
Keyword(s):  
Immune Response ◽  
Mrna Level ◽  
Thymic Stromal Lymphopoietin ◽  
Atopic Asthma ◽  
Chronic Obstructive ◽  
Strong Positive Correlation ◽  
Th2 Response ◽  
Airway Diseases ◽  
Th2 Immune Response ◽  
Obstructive Airway Diseases

Periostin and thymic stromal lymphopoietin (TSLP) are newly described markers of obstructive airway diseases and the mechanism by which both markers participate in immune response remains poorly understood. The aim of our study was to determine periostin and TSLP concentration in serum and induced sputum (IS) in patients with atopic asthma, chronic obstructive pulmonary disease (COPD), and controls, as well as to evaluate the potential link between periostin, TSLP, and Th2 immune response. Serum and IS levels of periostin, TSLP, IL-4, and IL-13 were determined in 12 atopic asthmatics, 16 COPD sufferers, and 10 controls. We noticed a significantly higher IS periostin and TSLP concentration at protein and mRNA level in asthmatics compared to the two other groups; additionally, periostin and TSLP were correlated positively with IS eosinophil count. A strong positive correlation between IS periostin and TSLP protein levels (r = 0.96) as well as mRNA expression level (r = 0.95) was found in patients with asthma. The results of our study show that periostin and TSLP are associated with eosinophilic airway inflammation and seem to be important drivers of atopic asthma but not COPD pathobiology. Very strong correlations between local periostin, TSLP, eosinophils, and IL-4 in asthma point to the link between periostin–TSLP and Th2 response.

scholarly journals Resistance to Haemonchus contortus in Corriedale sheep is associated to high parasite-specific IgA titer and a systemic Th2 immune response

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cecilia Escribano ◽  
Anderson Saravia ◽  
Monique Costa ◽  
Daniel Castells ◽  
Gabriel Ciappesoni ◽  
...  
Keyword(s):  
Immune Response ◽  
Haemonchus Contortus ◽  
Adaptive Immune Response ◽  
Gastrointestinal Nematode ◽  
Economic Losses ◽  
Th2 Response ◽  
Th2 Immune Response ◽  
Efficiency Of Selection ◽  
High Parasite ◽  
Selection Of

AbstractGastrointestinal nematode infections, including Haemonchus contortus, are one of the main causes of economic losses to ovine farmers worldwide. In order to contribute to the control of nematode infections and avoid parasite spreading we generated divergent resistant and susceptible sheep breeds and evaluated the adaptive immunity of these animals developed upon experimental infection against H. contortus. The selection of resistant or susceptible animals from the Corriedale Breed has been based on Expected Progeny Differences for faecal egg counts per gram. Furthermore, animals from the resistant Corriedale line were inseminated with imported semen from Australian Rylington Merino rams. Thus, the objective of this work was to analyze the adaptive immune response in both susceptible and resistant obtained lambs. Our results indicate that there is a potent parasite-specific local and systemic immune response in resistant animals and that although susceptible lambs can produce high levels of IgA antibodies during the infection, their antibody response is delayed which, together with an impaired specific-Th2 response, does not contribute to initial parasite elimination. Our results shed light into the immune mechanisms that mediate resistance to H. contortus and could constitute important assets to sheep farmers, not only as a means to detect resistance, but also to enhance the efficiency of selection in stud flocks.

scholarly journals Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

2004 ◽  
Vol 72 (1) ◽  
pp. 398-407 ◽  
Author(s):  
Salah Tawill ◽  
Laetitia Le Goff ◽  
Fahimeda Ali ◽  
Mark Blaxter ◽  
Judith E. Allen
Keyword(s):  
Immune Response ◽  
Critical Role ◽  
Interleukin 4 ◽  
Parasitic Nematodes ◽  
Mammalian Host ◽  
Phylogenetic Distance ◽  
Th2 Response ◽  
Free Living ◽  
Th2 Immune Response

ABSTRACT Infection with parasitic nematodes is characterized by the induction of a profound type 2 immune response. We have studied the role of glycans in the induction of the skewed type 2 response by antigens of the parasitic nematode Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph node cells from BALB/c mice immunized with soluble extracts of the two nematodes showed distinct antigen-specific proliferation and cytokine production; however, both nematodes induced antigen-specific interleukin 4 (IL-4) production, demonstrating that the induction of a biased type 2 response is not unique to parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes consistently induced significantly less IL-4 production than the respective mock-treated extracts, indicating that glycans play a critical role in the induction of the Th2 immune response by these nematodes. The glycan-dependent induction of the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data suggest that glycan determinants common to nematodes act as ligands, displaying distinct molecular patterns that trigger the immune system to launch a biased Th2 immune response upon exposure to these organisms or their products. Further, the similarity of our findings to those for Schistosoma mansoni egg antigen is striking considering the enormous phylogenetic distance between nematodes and trematodes. These data thus have important implications for how the mammalian host responds to widely divergent metazoan invaders and suggest that the powerful C. elegans model system can be used to address these questions.

scholarly journals The IL-33/ST2 Axis Is Associated with Human Visceral Leishmaniasis and Suppresses Th1 Responses in the Livers of BALB/c Mice Infected with Leishmania donovani

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Octavie Rostan ◽  
Jean-Pierre Gangneux ◽  
Claire Piquet-Pellorce ◽  
Christelle Manuel ◽  
Andrew N. J. McKenzie ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokine Signaling ◽  
Th2 Response ◽  
Content Type ◽  
Th1 Cytokines

ABSTRACT During visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both Th1 and Th2 components. Using enzyme-linked immunosorbent assay (ELISA) dosages, quantitative PCR (qPCR), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, during visceral leishmaniasis. We showed that a higher level of IL-33 was detected in the serum of patients with visceral leishmaniasis than in that from healthy donors and demonstrated the presence of IL-33+ cells in a liver biopsy specimen from a patient. Similarly, in BALB/c mice experimentally infected with L. donovani, a higher level of IL-33 was detected in the serum, as well as the presence of IL-33+ cells and ST2+ cells in the mouse liver. In ST2−/− BALB/c mice, better control of the hepatic parasite burden and reduced hepatomegaly were observed. This was associated with strong induction of Th1 cytokines (gamma interferon [IFN-γ] and IL-12) compared to the level in wild-type (WT) mice and better recruitment of myeloid cells associated with strongly induced chemokines (CCL2 and CXCL2) and receptors (CCR2 and CXCR2). Conversely, BALB/c mice treated twice weekly with recombinant IL-33 showed a dramatically reduced induction of Th1 cytokines and delayed inhibition of monocyte and neutrophil recruitment in the liver, which was associated with reduced KC/CXCL1 and CXCR2 expression. Taken together, our results suggest that IL-33 could be a new deleterious regulator of the hepatic immune response against Leishmania donovani, via the repression of the Th1 response and myeloid cell recruitment. IMPORTANCE Visceral leishmaniasis is a life-threatening systemic disease due to the Leishmania protozoa L. infantum and L. donovani and is ranked by the World Health Organization as the second most important protozoan parasitic disease after malaria for its grave morbidity, high mortality, and global distribution. Leishmania parasites subvert the host’s immune response to propagate to target organs, including the spleen, the bone marrow, and the liver. Control of hepatic parasite burdens depends on a delicate and poorly understood Th1/Th2 immune balance. To better understand this complex immune response, new cytokines are interesting targets for research studies. IL-33 is a newly described cytokine usually associated with Th2 response and involved in different diseases, including infectious diseases and hepatitis. Our results suggest that IL-33 could be a new factor of susceptibility and a potential prognostic marker during visceral leishmaniasis.

scholarly journals Synthesis of N-glycans implicated in asthma and allergy

2021 ◽  
Author(s):  
◽  
Gregory William Haslett
Keyword(s):  
Immune Response ◽  
Striking Similarity ◽  
Glycan Structure ◽  
Food Allergens ◽  
T Helper ◽  
Th2 Response ◽  
Th2 Immune Response ◽  
Asthma And Allergy ◽  
Allergen Extracts ◽  
The Relationship

<p>Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response.  This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.</p>

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