Select symbionts broadly drive high intestinal IgA levels
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PROVIDER: PRJEB59479 | ENA |
REPOSITORIES: ENA
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Project description:Ruminal ciliates both preys on and form symbiotic relationships with other members of the ruminal microbiota for their survival. However, it remains elusive if they have selectivity over their preys or symbionts. In the present study, we investigated the above selectivity by identifying and comparing the free-living prokaryotes (FLP) and the ciliate-associated prokaryotes (CAP) using Illumina MiSeq sequencing of 16S rRNA gene amplicons. We used single ciliates cells of both monocultures of Entodinium caudatum and Epidinium caudatum and eight different ciliate genera isolated from fresh rumen fluid of dairy cows. Irrespective of the source (laboratory monocultures vs. fresh isolates) of the single ciliate cells, the CAP significantly differed from the FLP in microbiota community profiles. Many bacterial taxa were either enriched or almost exclusively found in the CAP across most of the ciliate genera. A number of bacteria were also found for the first time as ruminal bacteria in the CAP. However, no clear difference was found in methanogens between the CAP and the FLP, which was confirmed using methanogen-specific qPCR. These results suggest that ruminal ciliates probably select their preys and symbionts, the latter of which has rarely been found among the free-living ruminal prokaryotes. The bacteria enriched or exclusively found in the CAP can be target bacteria to detect and localize using specific probes designed from their 16S rRNA sequences, to characterize using single-cell genomics, or to isolate using new media designed based on genomic information.
| S-EPMC6079354 | biostudies-literature
Project description:Rumen bacterial species belonging to the genera Butyrivibrio are important degraders of plant polysaccharides, particularly hemicelluloses (arabinoxylans) and pectin. Currently, four distinct species are recognized which have very similar substrate utilization profiles, but little is known about how these microorganisms are able to co-exist in the rumen. To investigate this question, Butyrivibrio hungatei MB2003 and Butyrivibrio proteoclasticus B316T were grown alone or in co-culture on the insoluble substrates, xylan or pectin, and their growth, release of sugars, fermentation end products and transcriptomes were examined. In single cultures, B316T was able to degrade and grow well on xylan and pectin, while MB2003 was unable to utilize either of these insoluble substrates to support significant growth. Co-cultures of B316T grown with MB2003 revealed that MB2003 showed almost equivalent growth to B316T when either xylan or pectin were supplied as substrates. The effect of co-culture on the transcriptomes of B316T and MB2003 was very marked; B316T transcription was largely unaffected by the presence MB2003, but MB2003 expressed a wide range of genes encoding carbohydrate degradation/metabolism and oligosaccharide transport/assimilation in order to compete with B316T for the released sugars. These results suggest that B316T has a role as an initiator of the primary solubilization of xylan and pectin, while MB2003 competes effectively as a scavenger for the released soluble sugars to enable its growth and maintenance in the rumen.
2018-09-27 | GSE120544 | GEO
Project description:We investigated the mucosal distribution and neutralization potency of rhesus recombinant versions of the HIV-specific, broadly neutralizing antibody b12 (RhB12) following intravenous administration to lactating rhesus monkeys. IgG and dimeric IgA (dIgA) administration resulted in high plasma concentrations of broadly neutralizing antibody (bnAb), but the monomeric IgA (mIgA) was rapidly cleared from the systemic compartment. Interestingly, differences in the distribution of the RhB12 isoform were observed between the mucosal compartments. The peak concentration of RhB12 IgG was higher than dIgA in saliva, rectal, and vaginal secretions, but the bnAb concentration in milk was one to two logs higher after dIgA administration than with IgG or mIgA infusion. Neutralization was observed in plasma of all animals, but only those infused with RhB12 dIgA showed moderate levels of virus neutralization in milk. Remarkably, virus-specific secretory IgA was detected in mucosal compartments following dIgA administration. The high milk RhB12 dIgA concentration suggests that passive immunization with dIgA could be more effective than IgG to inhibit virus in breast milk.
| S-EPMC5063654 | biostudies-literature
Project description:Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. To precisely engineer bnAb boosting immunogens, we used molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identified Env mutations that were predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encoded antibody affinity gains and selected for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.
| S-EPMC10760096 | biostudies-literature
Project description:Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identify Env mutations predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encode antibody affinity gains and select for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.
| S-EPMC11532496 | biostudies-literature
Project description:The role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138-IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ-/- mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells. Although IL-21R-/- mice or IL-17R-/- mice showed decreased Ag-specific memory IgA production in the intestines upon infection with Citrobacter rodentium, the percentage of IgA+CD38+CD138- memory B cells in Peyer's patches and LP was decreased only in IL-21R-/- mice, but not in IL-17R-/- mice, after reinfection with C. rodentium compared with wild-type mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138- memory B cells in Peyer's patches and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Aicda and Ski expression was decreased in B cells of IL-21R-/- mice after C. rodentium reinfection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through upregulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.
| S-EPMC7898419 | biostudies-literature
Project description:Although processed potato tuber texture is an important trait that influences consumer preference, a detailed understanding of tuber textural properties at the molecular level is lacking. Previous work has identified tuber pectin methyl esterase activity (PME) as a potential factor impacting on textural properties and the expression of a gene encoding an isoform of PME (PEST1) was associated with cooked tuber textural properties. In this study a transgenic approach was undertaken to investigate further the impact of the PEST1 gene. Antisense and over-expressing potato lines were generated. In over-expressing lines tuber PME activity was enhanced by up to 2.3 fold whereas in antisense lines PME activity was decreased by up to 38%. PME isoform analysis indicated that the PEST1 gene encoded one isoform of PME. Analysis of cell walls from tubers from the over-expressing lines indicated that the changes in PME activity resulted in a decrease in pectin methylation. Analysis of processed tuber texture demonstrated that the reduced level of pectin methylation in the over-expressing transgenic lines was associated with a firmer processed texture. Thus there is a clear link between PME activity, pectin methylation and processed tuber textural properties.
2010-12-01 | E-TABM-1062 | biostudies-arrayexpress
Project description:In addition to direct neutralization and other classical effector functions, IgG possesses a little recognized and thus under-utilized effector function at mucosal surfaces: Fc-mucin bonds enable IgG to trap viruses in mucus. Due to the paucity of envelope glycoproteins that limits the number of IgG that can bind HIV, it remains poorly understood whether IgG-mucin interactions can effectively immobilize HIV in human cervicovaginal mucus (CVM). Here, we obtained 54 fresh, undiluted CVM specimens from 17 different women, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent HIV virus-like-particles in CVM treated with various HIV-specific IgG. We observed consistent and effective trapping of HIV by broadly neutralizing antibodies (VRC01, PGT121, and 2F5) in a subset of women. While trapping efficacy was not affected by the menstrual cycle, it was positively correlated with appreciable L. Crispatus populations in the microbiome, and negatively correlated with appreciable L. Iners or G. Vaginalis populations. Our work demonstrates for the first time that IgG-mucin crosslinking is capable of reinforcing the mucosal barrier against HIV, and motivates further investigation of passive immunization against vaginal transmission of STIs. STATEMENT OF SIGNIFICANCE: HIV transmission in women primarily occurs vaginally, yet the 3-way interactions between mucins and HIV virions mediated by HIV-binding antibodies in cervicovaginal mucus (CVM) is not well understood. While IgG-Fc possess weak affinity to mucins that trap virus/IgG complexes in mucus, the effectiveness against HIV remains unclear, due to the low number of virion-bound IgG. Here, we discovered that IgG can trap HIV consistently in CVM from select individuals regardless of their birth control status or menstrual cycle phase. IgG-mediated trapping of HIV was moderately associated with microbiome composition. These results suggest that IgG-mucin interactions could potentially reduce HIV transmission and highlight the importance of mucosal secretions in antibody-mediated prevention of HIV and other sexually transmitted infections.
| S-EPMC10619885 | biostudies-literature
Project description:ObjectiveIgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children's age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity.MethodsA total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer.ResultsApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level < 24.81 mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients.ConclusionsSerum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR = 0.32, 95%CI = 0.12-0.85, p = 0.023) was identified as a protective factor for nephritis in all lgAV patients.
| S-EPMC6927057 | biostudies-literature
Project description:BackgroundThe neuropeptide vasoactive intestinal peptide (VIP) is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions.ResultsIn the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice.ConclusionTogether these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.
| S-EPMC2474849 | biostudies-literature