scholarly journals Escherichia coli Nissle 1917 administered as a dextranomar microsphere biofilm enhances immune responses against human rotavirus in a neonatal malnourished pig model colonized with human infant fecal microbiota

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246193
Author(s):  
Husheem Michael ◽  
Francine C. Paim ◽  
Ayako Miyazaki ◽  
Stephanie N. Langel ◽  
David D. Fischer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dendritic Cells ◽  
B Cells ◽  
Immune Responses ◽  
Killer Cell ◽  
Fecal Microbiota ◽  
Pig Model ◽  
Human Infant ◽  
Human Rotavirus ◽  
Iga Antibody

Human rotavirus (HRV) is a leading cause of diarrhea in children. It causes significant morbidity and mortality, especially in low- and middle-income countries (LMICs), where HRV vaccine efficacy is low. The probiotic Escherichia coli Nissle (EcN) 1917 has been widely used in the treatment of enteric diseases in humans. However, repeated doses of EcN are required to achieve maximum beneficial effects. Administration of EcN on a microsphere biofilm could increase probiotic stability and persistence, thus maximizing health benefits without repeated administrations. Our aim was to investigate immune enhancement by the probiotic EcN adhered to a dextranomar microsphere biofilm (EcN biofilm) in a neonatal, malnourished piglet model transplanted with human infant fecal microbiota (HIFM) and infected with rotavirus. To create malnourishment, pigs were fed a reduced amount of bovine milk. Decreased HRV fecal shedding and protection from diarrhea were evident in the EcN biofilm treated piglets compared with EcN suspension and control groups. Moreover, EcN biofilm treatment enhanced natural killer cell activity in blood mononuclear cells (MNCs). Increased frequencies of activated plasmacytoid dendritic cells (pDC) in systemic and intestinal tissues and activated conventional dendritic cells (cDC) in blood and duodenum were also observed in EcN biofilm as compared with EcN suspension treated pigs. Furthermore, EcN biofilm treated pigs had increased frequencies of systemic activated and resting/memory antibody forming B cells and IgA+ B cells in the systemic tissues. Similarly, the mean numbers of systemic and intestinal HRV-specific IgA antibody secreting cells (ASCs), as well as HRV-specific IgA antibody titers in serum and small intestinal contents, were increased in the EcN biofilm treated group. In summary EcN biofilm enhanced innate and B cell immune responses after HRV infection and ameliorated diarrhea following HRV challenge in a malnourished, HIFM pig model.

scholarly journals Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model

Vaccine ◽  
2018 ◽  
Vol 36 (42) ◽  
pp. 6270-6281 ◽  
Author(s):  
Ayako Miyazaki ◽  
Sukumar Kandasamy ◽  
Husheem Michael ◽  
Stephanie N. Langel ◽  
Francine C. Paim ◽  
...  
Keyword(s):  
Fecal Microbiota ◽  
Protein Deficiency ◽  
Pig Model ◽  
Human Infant ◽  
Rotavirus Vaccine ◽  
Human Rotavirus ◽  
Gnotobiotic Pig

scholarly journals Escherichia coli Nissle 1917 Enhances Innate and Adaptive Immune Responses in a Ciprofloxacin-Treated Defined-Microbiota Piglet Model of Human Rotavirus Infection

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Husheem Michael ◽  
Francine C. Paim ◽  
Stephanie N. Langel ◽  
Ayako Miyazaki ◽  
David D. Fischer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
B Cells ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Specific Antibody ◽  
T Helper ◽  
Cytotoxic Cells ◽  
Commensal Microbiota ◽  
Human Rotavirus ◽  
Enteric Infections

ABSTRACT Human rotavirus (HRV) infection is a major cause of gastroenteritis in children worldwide. Broad-spectrum antibiotic-induced intestinal microbial imbalance and the ensuing immune-metabolic dysregulation contribute to the persistence of HRV diarrhea. Escherichia coli Nissle 1917 (EcN), a Gram-negative probiotic, was shown to be a potent immunostimulant and alleviated HRV-induced diarrhea in monocolonized gnotobiotic (Gn) piglets. Our goal was to determine how EcN modulates immune responses in ciprofloxacin (Cipro)-treated Gn piglets colonized with a defined commensal microbiota (DM) and challenged with virulent HRV (VirHRV). Cipro given in therapeutic doses for a short term reduced serum and intestinal total and HRV-specific antibody titers, while EcN treatment alleviated this effect. Similarly, EcN treatment increased the numbers of total immunoglobulin-secreting cells, HRV-specific antibody-secreting cells, activated antibody-forming cells, resting/memory antibody-forming B cells, and naive antibody-forming B cells in systemic and/or intestinal tissues. Decreased levels of proinflammatory but increased levels of immunoregulatory cytokines and increased frequencies of Toll-like receptor-expressing cells were evident in the EcN-treated VirHRV-challenged group. Moreover, EcN treatment increased the frequencies of T helper and T cytotoxic cells in systemic and/or intestinal tissues pre-VirHRV challenge and the frequencies of T helper cells, T cytotoxic cells, effector T cells, and T regulatory cells in systemic and/or intestinal tissues postchallenge. Moreover, EcN treatment increased the frequencies of systemic and mucosal conventional and plasmacytoid dendritic cells, respectively, and the frequencies of systemic natural killer cells. Our findings demonstrated that Cipro use altered immune responses of DM-colonized neonatal Gn pigs, while EcN supplementation rescued these immune parameters partially or completely. IMPORTANCE Rotavirus (RV) is a primary cause of malabsorptive diarrhea in children and is associated with significant morbidity and mortality, especially in developing countries. The use of antibiotics exacerbates intestinal microbial imbalance and results in the persistence of RV-induced diarrhea. Probiotics are now being used to treat enteric infections and ulcerative colitis. We showed previously that probiotics partially protected gnotobiotic (Gn) piglets against human RV (HRV) infection and decreased the severity of diarrhea by modulating immune responses. However, the interactions between antibiotic and probiotic treatments and HRV infection in the context of an established gut microbiota are poorly understood. In this study, we developed a Gn pig model to study antibiotic-probiotic-HRV interactions in the context of a defined commensal microbiota (DM) that mimics aspects of the infant gut microbiota. Our results provide valuable information that will contribute to the treatment of antibiotic- and/or HRV-induced diarrhea and may be applicable to other enteric infections in children.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

scholarly journals The Role of Dendritic Cells, B Cells, and M Cells in Gut-Oriented Immune Responses

2001 ◽  
Vol 166 (8) ◽  
pp. 4843-4852 ◽  
Author(s):  
Oral Alpan ◽  
Gregory Rudomen ◽  
Polly Matzinger
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Immune Responses ◽  
M Cells

scholarly journals Mucosal and Systemic Immune Responses in Patients with Diarrhea Due to CS6-Expressing Enterotoxigenic Escherichia coli

2007 ◽  
Vol 75 (5) ◽  
pp. 2269-2274 ◽  
Author(s):  
Firdausi Qadri ◽  
Tanvir Ahmed ◽  
Firoz Ahmed ◽  
M. Saruar Bhuiyan ◽  
Mohammad Golam Mostofa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Protein A ◽  
Enterotoxigenic Escherichia Coli ◽  
Severe Dehydration ◽  
Colonization Factor ◽  
Disease Spectrum ◽  
Iga Antibodies ◽  
Iga Antibody ◽  
Antibody Secreting Cells

ABSTRACTColonization factor CS6 expressed by enterotoxigenicEscherichia coli(ETEC) is a nonfimbrial polymeric protein. A substantial proportion of ETEC strains isolated from patients in endemic settings and in people who travel to regions where ETEC is endemic are ETEC strains expressing CS6, either alone or in combination with fimbrial colonization factor CS5 or CS4. However, relatively little is known about the natural immune responses elicited against CS6 expressed by ETEC strains causing disease. We studied patients who were hospitalized with diarrhea (n= 46) caused by CS6-expressing ETEC (ETEC expressing CS6 or CS5 plus CS6) and had a disease spectrum ranging from severe dehydration (27%) to moderate or mild dehydration (73%). Using recombinant CS6 antigen, we found that more than 90% of the patients had mucosal immune responses to CS6 expressed as immunoglobulin (IgA) antibody-secreting cells (ASC) or antibody in lymphocyte supernatant (ALS) and that about 57% responded with CS6-specific IgA antibodies in feces. More than 80% of the patients showed IgA seroconversion to CS6. Significant increases in the levels of anti-CS6 antibodies of the IgG isotype were also observed in assays for ASC (75%), ALS (100%), and serum (70%). These studies demonstrated that patients hospitalized with the noninvasive enteric pathogen CS6-expressing ETEC responded with both mucosal and systemic antibodies against CS6. Studies are needed to determine if the anti-CS6 responses protect against reinfection and if protective levels of CS6 immunity are induced by vaccination.

scholarly journals Prenatally Acquired Vitamin A Deficiency Alters Innate Immune Responses to Human Rotavirus in a Gnotobiotic Pig Model

2013 ◽  
Vol 190 (9) ◽  
pp. 4742-4753 ◽  
Author(s):  
Anastasia N. Vlasova ◽  
Kuldeep S. Chattha ◽  
Sukumar Kandasamy ◽  
Christine S. Siegismund ◽  
Linda J. Saif
Keyword(s):  
Vitamin A ◽  
Immune Responses ◽  
Vitamin A Deficiency ◽  
Innate Immune ◽  
Pig Model ◽  
Innate Immune Responses ◽  
Human Rotavirus ◽  
Gnotobiotic Pig

scholarly journals Intestinal Immune Responses to an Inactivated Oral Enterotoxigenic Escherichia coli Vaccine and Associated Immunoglobulin A Responses in Blood

1998 ◽  
Vol 66 (7) ◽  
pp. 3311-3316 ◽  
Author(s):  
Christina Åhrén ◽  
Marianne Jertborn ◽  
Ann-Mari Svennerholm
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Serum Antibody ◽  
Immunoglobulin A ◽  
Lavage Fluid ◽  
Antibody Responses ◽  
Enterotoxigenic Escherichia Coli ◽  
Antibody Secreting Cell ◽  
Colonization Factor ◽  
Iga Antibody

ABSTRACT An inactivated oral enterotoxigenic Escherichia coli(ETEC) vaccine against ETEC diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage fluid to CTB and CFAs were determined and compared with corresponding responses in stool extracts and serum as well as with IgA antibody-secreting cell (ASC) responses in peripheral blood. Two doses of vaccine induced significant IgA responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and in stool in 38 to 81% of them. The most frequent responses were seen against CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool correlated significantly (CTB,P < 0.01; CFA/I, P < 0.05) with those in intestinal lavage. Intestinal lavage responses against CFAs were best reflected by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%, followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7 to 65%) analyses. CTB-specific immune responses were seen in >90% of the vaccinees in all assays.

scholarly journals SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best

2021 ◽  
Author(s):  
Ane Fernandez Salinas ◽  
Eva Piano Mortari ◽  
Sara Terreri ◽  
Concetta Quintarelli ◽  
Federica Pulvirenti ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Vaccine Dose ◽  
Memory B Cells ◽  
Cell Responses ◽  
Specific Memory ◽  
Immune Deficiencies ◽  
Iga Antibody ◽  
Specific Igg

Abstract Background Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. Results The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. Conclusion In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.

scholarly journals Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant

2017 ◽  
Vol 24 (8) ◽  
Author(s):  
David D. Fischer ◽  
Sukumar Kandasamy ◽  
Francine C. Paim ◽  
Stephanie N. Langel ◽  
Moyasar A. Alhamo ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Fecal Microbiota ◽  
Human Infant ◽  
Converting Enzyme ◽  
Deficient Diet ◽  
Fecal Microbiota Transplant ◽  
Rotavirus Infection ◽  
Adaptive Immune ◽  
Human Rotavirus ◽  
Gnotobiotic Pigs

ABSTRACT Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of 5 years. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets and infected with virulent human rotavirus (HRV). After human rotavirus infection, protein-deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+ CD4+) and cytotoxic T (CD3+ CD8+) lymphocyte frequencies, and serum tryptophan and angiotensin I-converting enzyme 2. Additionally, deficient-diet pigs had impaired tryptophan catabolism postinfection compared with sufficient-diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus-infected, sufficient- and deficient-diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4+ or CD8+ CD25+ FoxP3+) T cells in pigs on both the sufficient and the deficient diets. These results suggest that a protein-deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.

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