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 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 IL-10-Producing B Cells Regulate T Helper Cell Immune Responses during 1,3-β-Glucan-Induced Lung Inflammation

2017 ◽  
Vol 8 ◽  
Author(s):  
Fangwei Liu ◽  
Xiaowei Lu ◽  
Wujing Dai ◽  
Yiping Lu ◽  
Chao Li ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Lung Inflammation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

scholarly journals An OMV-Based Nanovaccine Confers Safety and Protection against Pathogenic Escherichia coli via Both Humoral and Predominantly Th1 Immune Responses in Poultry

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2293
Author(s):  
Rujiu Hu ◽  
Haojing Liu ◽  
Mimi Wang ◽  
Jing Li ◽  
Hua Lin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Specific Antibody ◽  
Bacterial Infections ◽  
Outer Membrane Vesicles ◽  
Economic Losses ◽  
Broiler Chicks ◽  
Immunological Mechanism ◽  
Pathogenic Escherichia Coli

Avian pathogenic Escherichia coli (APEC) infection in poultry causes enormous economic losses and public health risks. Bacterial outer membrane vesicles (OMVs) and nano-sized proteolipids enriched with various immunogenic molecules have gained extensive interest as novel nanovaccines against bacterial infections. In this study, after the preparation of APEC O2-derived OMVs (APEC_OMVs) using the ultracentrifugation method and characterization of them using electron microscopy and nanoparticle tracking analyses, we examined the safety and vaccination effect of APEC_OMVs in broiler chicks and investigated the underlying immunological mechanism of protection. The results showed that APEC_OMVs had membrane-enclosed structures with an average diameter of 89 nm. Vaccination with 50 μg of APEC_OMVs had no side effects and efficiently protected chicks against homologous infection. APEC_OMVs could be effectively taken up by chicken macrophages and activated innate immune responses in macrophages in vitro. APEC_OMV vaccination significantly improved activities of serum non-specific immune factors, enhanced the specific antibody response and promoted the proliferation of splenic and peripheral blood lymphocytes in response to mitogen. Furthermore, APEC_OMVs also elicited a predominantly IFN-γ-mediated Th1 response in splenic lymphocytes. Our data revealed the involvement of both non-specific immune responses and specific antibody and cytokine responses in the APEC_OMV-mediated protection, providing broader knowledge for the development of multivalent APEC_OMV-based nanovaccine with high safety and efficacy in the future.

scholarly journals Systemic and local immune responses againstHelicobacter pylori urease in patients with chronic gastritis: distinct IgA and IgG productive sites

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 168-175 ◽  
Author(s):  
S Futagami ◽  
H Takahashi ◽  
Y Norose ◽  
M Kobayashi
Keyword(s):  
B Cells ◽  
Gastric Mucosa ◽  
Immune Responses ◽  
Atrophic Gastritis ◽  
Gastric Juice ◽  
Chronic Gastritis ◽  
Specific Antibody ◽  
Histopathological Analysis ◽  
Grade Ii ◽  
H Pylori

Background—Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pyloriinfected patients.Aims—To analyse the relation between systemic and local humoral immune responses toH pylori urease and grades of chronic gastritis.Patients—Seventy five patients with chronic gastritis associated with H pyloriinfection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active).Methods—Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis.Results—In the sera of patients with grade I gastritis, weak IgG but relatively strong IgA responses toH pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy.Conclusions—PurifiedH pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis ofH pylori infection.

scholarly journals Defective SARS-CoV-2 immune responses in an immunocompromised individual with prolonged viral replication

2021 ◽  
Author(s):  
Claire L Gordon ◽  
Olivia C Smibert ◽  
Natasha E Holmes ◽  
Kyra Y L Chua ◽  
Rose Morgan ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Responses ◽  
Viral Replication ◽  
Specific Antibody ◽  
Late Onset ◽  
Antibody Responses ◽  
Hla Dr ◽  
Immunocompromised Individual ◽  
Immunocompromised Hosts

Abstract We describe SARS-CoV-2-specific immune responses in a patient with lymphoma and recent PD-1 inhibitor therapy with late onset of severe COVID-19 disease and prolonged SARS-CoV-2 replication, in comparison to age-matched and immunocompromised controls. High levels of HLA-DR +/CD38 +-activation, IL-6 and IL-18 in the absence of B cells and PD-1 expression was observed. SARS-CoV-2-specific antibody responses were absent and SARS-CoV-2 specific T cells were minimally detected. This case highlights challenges in managing immunocompromised hosts who may fail to mount effective virus-specific immune responses.

scholarly journals Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition.

1978 ◽  
Vol 148 (4) ◽  
pp. 871-877 ◽  
Author(s):  
H Cantor ◽  
J Hugenberger ◽  
L McVay-Boudreau ◽  
D D Eardley ◽  
J Kemp ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Inhibitory Activity ◽  
T Helper Cells ◽  
Feedback Inhibition ◽  
T Helper ◽  
Surface Phenotype ◽  
Helper Cells

Purified Ly1 cells induce other T-cell sets to exert potent feedback inhibitory activity and this T-T interaction has been shown to play an important role in regulating in vivo immune responses. Approximately 2/3 of Ly1 cells also express the Qa1 surface phenotype (Ly1:Qa1+ cells). The experiments reported here indicate that Ly1:Qal+ cells are responsible for induction of feedback inhibition and that signals from both Ly1:Qal+ cells and Ly1:Qal- cells are required for optimal formation of antibody by B cells.

scholarly journals The gut microbiota and development of Vibrio cholerae -specific long-term memory B cells in adults after whole-cell killed oral cholera vaccine

2021 ◽  
Author(s):  
Denise Chac ◽  
Taufiqur R. Bhuiyan ◽  
Amit Saha ◽  
Mohammad M. Alam ◽  
Umme Salma ◽  
...  
Keyword(s):  
B Cells ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Vibrio Cholerae ◽  
Memory B Cells ◽  
Health Concern ◽  
Cholera Vaccine ◽  
Vaccine Adjuvants ◽  
Oral Cholera Vaccine

Cholera is a diarrheal disease caused by Vibrio cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. cholerae and may be a major determinant of long-term protection from cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may “prime” the mucosal immune response to vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.

scholarly journals Helminth Protein Vaccine Induced Follicular T Helper Cell for Enhancement of Humoral Immunity againstSchistosoma japonicum

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Jingyao Zhang ◽  
Wenjuan Gao ◽  
Qirui Guo ◽  
Bobo Huang ◽  
Bin Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Molecular Targets ◽  
T Helper Cell ◽  
Protein Vaccine ◽  
T Helper ◽  
Humoral Immune ◽  
Tfh Cells ◽  
Humoral Immune Responses

Protein vaccines combined with adjuvants have been widely used to induce immune responses, especially the humoral immune response, against molecular targets including parasites. Follicular T helper (Tfh) cells are the specialized providers of B-cell help, however, the induction of Tfh cells in protein vaccination has been rarely studied. Here, we report that theSchistosoma japonicumrecombinant protein (SjGST-32) combined with tacrolimus (FK506) augmented the induction of Tfh cells, which expressed the canonical markers CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice. Furthermore, the expression of IL-21R on germinal center (GC) B cells and memory B cells increased in immunized mice, which indicated that IL-21 from the induced Tfh cells interacted with IL-21R for activation of B cells and maintenance of long-lived humoral immunity. Our results suggest that helminth protein vaccine combined with FK506 induces Tfh cell for stimulating humoral immune responses and inducing long-lived humoral immunity.

scholarly journals Ia-mediated signal transduction leads to proliferation of primed B lymphocytes.

1989 ◽  
Vol 170 (3) ◽  
pp. 877-886 ◽  
Author(s):  
J C Cambier ◽  
K R Lehmann
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
B Lymphocytes ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Contact ◽  
T Helper ◽  
Th Lymphocytes

One of the most controversial questions in immunology is the molecular basis by which Th lymphocytes deliver activating signals to quiescent B lymphocytes during T cell-dependent immune responses. Recent studies suggest that T cell-dependent activation of quiescent B lymphocytes may involve signaling mediated by direct T helper cell-B cell contact. Since B cell membrane-associated MHC-encoded class II molecules (Ia) must be recognized by Th lymphocytes for generation of T cell-dependent humoral immune responses, they are obvious candidates for receptors of this signal. Here we report that stimulation of quiescent murine B cells with IL-4 and antibodies against the B cell antigen receptor for 12-16 h primes cells to proliferate in response to immobilized mIa binding ligands. In the presence of additional lymphokines, these B cells differentiate to secrete Ig of IgM and IgG classes. These results suggest that Ia molecules are receptors for direct, T helper cell-B cell contact mediated signaling that results in B cell proliferation.

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