scholarly journals Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

2021 ◽  
Author(s):  
Hugo A Penny ◽  
Rita G Domingues ◽  
Maria Z Krauss ◽  
Felipe Melo-Gonzalez ◽  
Suzanna Dickson ◽  
...  
Keyword(s):  
Microbial Community ◽  
Immune Responses ◽  
Metabolic Activity ◽  
Intestinal Tract ◽  
Plasma Cells ◽  
Commensal Microbiota ◽  
Commensal Species ◽  
A Cell ◽  
Intestinal Iga ◽  
Diurnal Regulation

Mutualistic interactions with the commensal microbiota are enforced through a range of immune responses that confer metabolic benefits for the host and ensure tissue health and homeostasis. Immunoglobulin (Ig)A responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation by dietary-derived metabolic cues and a cell-intrinsic circadian clock. Rhythmicity in IgA secretion conferred oscillatory patterns on the commensal microbial community and its associated metabolic activity, resulting in changes to metabolite availability over the course of the circadian day. Our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota align to ensure metabolic health.

scholarly journals The Wanderings of Gut-Derived IgA Plasma Cells: Impact on Systemic Immune Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Selina J. Keppler ◽  
Marie Christine Goess ◽  
Julia M. Heinze
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
B Cell ◽  
Protective Immunity ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Commensal Microbiota ◽  
Mucosal Tissues ◽  
Iga Antibodies ◽  
Antibody Secreting Cells

Humoral immunity is mainly mediated by a B cell population highly specialized to synthesize and secrete large quantities of antibodies – the antibody-secreting cells (ASC). In the gastrointestinal environment, a mixture of foreign antigens from the diet, commensal microbiota as well as occasional harmful pathogens lead to a constant differentiation of B cells into ASC. Due to this permanent immune response, more than 80% of mammalian ASC reside in the gut, of which most express immunoglobulin A (IgA). IgA antibodies contribute to intestinal homeostasis and can mediate protective immunity. Recent evidence points at a role for gut-derived ASC in modulating immune responses also outside of mucosal tissues. We here summarize recent evidence for wandering ASC, their antibodies and their involvement in systemic immune responses.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

scholarly journals Understanding Cell Interactions Using Modular Nanoparticle Libraries

2019 ◽  
Vol 72 (8) ◽  
pp. 595 ◽  
Author(s):  
Georgina K. Such ◽  
Angus P. R. Johnston
Keyword(s):  
Immune Responses ◽  
Small Molecules ◽  
Active Form ◽  
Reticuloendothelial System ◽  
Endosomal Escape ◽  
Biological Interactions ◽  
Nanoparticle Delivery ◽  
A Cell ◽  
Nanoparticle Structure ◽  
The Right

Nanoparticle delivery systems have significant potential to facilitate the delivery of novel therapeutics, such as proteins, DNA or small molecules. However, there are multiple biological barriers that need to be overcome to deliver the cargo in an active form. These challenges include evading clearance by the reticuloendothelial system, minimising adverse immune responses, targeting specific cells and tissues, and trafficking into the right compartment of the cell. In this account, we will discuss how nanoparticle structure can be tuned to optimise biological interactions and thus improve the ability of nanoparticles to overcome these barriers. The focus of this article will be on controlling cell targeting and trafficking within a cell, e.g. endosomal escape.

scholarly journals Murine myeloid cell MCPIP1 suppresses autoimmunity by regulating B-cell expansion and differentiation

2021 ◽  
Vol 14 (3) ◽  
pp. dmm047589
Author(s):  
Ewelina Dobosz ◽  
Georg Lorenz ◽  
Andrea Ribeiro ◽  
Vivian Würf ◽  
Marta Wadowska ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Immune Responses ◽  
Cell Activation ◽  
Plasma Cells ◽  
Myeloid Cell ◽  
Skin Inflammation ◽  
Adaptive Immune ◽  
Systemic Autoimmunity ◽  
Key Factor ◽  
Old Mice

ABSTRACTMyeloid-derived cells, in particular macrophages, are increasingly recognized as critical regulators of the balance of immunity and tolerance. However, whether they initiate autoimmune disease or perpetuate disease progression in terms of epiphenomena remains undefined.Here, we show that depletion of MCPIP1 in macrophages and granulocytes (Mcpip1fl/fl-LysMcre+ C57BL/6 mice) is sufficient to trigger severe autoimmune disease. This was evidenced by the expansion of B cells and plasma cells and spontaneous production of autoantibodies, including anti-dsDNA, anti-Smith and anti-histone antibodies. Consequently, we document evidence of severe skin inflammation, pneumonitis and histopathologic evidence of glomerular IgG deposits alongside mesangioproliferative nephritis in 6-month-old mice. These phenomena are related to systemic autoinflammation, which secondarily induces a set of cytokines such as Baff, Il5, Il9 and Cd40L, affecting adaptive immune responses. Therefore, abnormal macrophage activation is a key factor involved in the loss of immune tolerance.Overall, we demonstrate that deficiency of MCPIP1 solely in myeloid cells triggers systemic lupus-like autoimmunity and that the control of myeloid cell activation is a crucial checkpoint in the development of systemic autoimmunity.

scholarly journals T-independent antigen induces humoral memory through germinal centers

2022 ◽  
Vol 219 (3) ◽  
Author(s):  
Xin Liu ◽  
Yongshan Zhao ◽  
Hai Qi
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Germinal Center ◽  
Plasma Cells ◽  
Underlying Mechanism ◽  
Memory B Cells ◽  
Antigen B ◽  
Per Se ◽  
Humoral Responses ◽  
Human And Mouse

T-dependent humoral responses generate long-lived memory B cells and plasma cells (PCs) predominantly through germinal center (GC) reaction. In human and mouse, memory B cells and long-lived PCs are also generated during immune responses to T-independent antigen, including bacterial polysaccharides, although the underlying mechanism for such T-independent humoral memory is not clear. While T-independent antigen can induce GCs, they are transient and thought to be nonproductive. Unexpectedly, by genetic fate-mapping, we find that these GCs actually output memory B cells and PCs. Using a conditional BCL6 deletion approach, we show memory B cells and PCs fail to last when T-independent GCs are precluded, suggesting that the GC experience per se is important for programming longevity of T-independent memory B cells and PCs. Consistent with the fact that infants cannot mount long-lived humoral memory to T-independent antigen, B cells from young animals intrinsically fail to form T-independent GCs. Our results suggest that T-independent GCs support humoral memory, and GC induction may be key to effective vaccines with T-independent antigen.

scholarly journals SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Adaptive Immune Response ◽  
Antibody Assay ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Previous Infection ◽  
A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

scholarly journals Correlation between water activity (aw) and microbial epiphytic communities associated with grapes berries

OENO One ◽  
2020 ◽  
Vol 54 (1) ◽  
pp. 49-61
Author(s):  
Guilherme Eduardo Martins ◽  
Cosimo Casini ◽  
Jean-Pierre Da Costa ◽  
Laurence Geny ◽  
Aline Lonvaud ◽  
...  
Keyword(s):  
Microbial Community ◽  
Water Activity ◽  
Metabolic Activity ◽  
Grape Berries ◽  
Lack Of Information ◽  
Grape Quality ◽  
Complex Microbial Community ◽  
Grape Skins ◽  
Physiological Profiles ◽  
Epiphytic Communities

Grape berries host a complex microbial community that plays a predominant role in grape quality prior to harvest and in the winemaking process. Like other carpospheric habitats, the epiphytic microbial community of grape berries is influenced by several factors. Climate plays an essential role in grape composition and quality, and its impact on berry microbiota was recently demonstrated. However, there is still a lack of information about how environmental conditions influence the system in grape berries.In this study, the microbial communities of grape berries from two wine appellations characterized by specific climatological conditions were analyzed. The results revealed that the size of cultivable communities (bacteria, yeast and filamentous fungi) and the diversity and richness of the microbial community profiles were higher in vineyards found to have lower temperatures. The metabolic activity (Community-Level Physiological Profiles) of the epiphytic microbial community was lower in warm climates. Water activity (aw) had a positive effect on the cultivable population, on metabolic activity, and on microbial diversity.The results showed that the microclimate affects the microbial population associated with grape berries through the aw of grape skins.

Blood-borne human plasma cells in steady state are derived from mucosal immune responses

Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2461-2469 ◽  
Author(s):  
Henrik E. Mei ◽  
Taketoshi Yoshida ◽  
Wondossen Sime ◽  
Falk Hiepe ◽  
Kathi Thiele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Immune Responses ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Low Frequency ◽  
Substantial Contribution ◽  
Immune Reactions ◽  
Humoral Immune ◽  
Humoral Immune Responses

AbstractProviding humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule β7 integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10+ plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA+, nonmigratory, and express β7 integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG+ cells appear in blood, both CD62L+, β7 integrin−, dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L− plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA+ plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other.

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