scholarly journals Receptor-mediated Immunoglobulin G Transport Across Mucosal Barriers in Adult Life

2002 ◽  
Vol 196 (3) ◽  
pp. 303-310 ◽  
Author(s):  
Gerburg M. Spiekermann ◽  
Patricia W. Finn ◽  
E. Sally Ward ◽  
Jennifer Dumont ◽  
Bonny L. Dickinson ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Adult Life ◽  
Secretory Iga ◽  
Mouse Lung ◽  
Bronchial Epithelial ◽  
Mucosal Surfaces ◽  
Dependent Absorption ◽  
Epithelial Barriers ◽  
Mucosal Secretions

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain the immunoglobulins (Ig)G and secretory IgA (sIgA) that function together in host defense. Exactly how IgG crosses epithelial barriers to function in mucosal immunity remains unknown. Here, we test the idea that the MHC class I–related Fc-receptor, FcRn, transports IgG across the mucosal surface of the human and mouse lung from lumen to serosa. We find that bronchial epithelial cells of the human, nonhuman primate, and mouse, express FcRn in adult-life, and demonstrate FcRn-dependent absorption of a bioactive Fc-fusion protein across the respiratory epithelium of the mouse in vivo. Thus, IgG, like dimeric IgA, can cross epithelial barriers by receptor-mediated transcytosis in adult animals. These data show that mucosal surfaces that express FcRn reabsorb IgG and explain a mechanism by which IgG may act in immune surveillance to retrieve lumenal antigens for processing in the lamina propria or systemically.

scholarly journals Secretory IgA N-glycans contribute to the protection against E. coli O55 infection of germ-free piglets

2020 ◽  
Author(s):  
Leona Raskova Kafkova ◽  
Diana Brokesova ◽  
Michal Krupka ◽  
Zuzana Stehlikova ◽  
Jiri Dvorak ◽  
...  
Keyword(s):  
Clinical Status ◽  
Secretory Component ◽  
Secretory Iga ◽  
Intestinal Histology ◽  
E Coli ◽  
Germ Free ◽  
Mucosal Surfaces ◽  
Species Specific

Abstract Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets’ intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.

scholarly journals Recombinant neutralizing secretory IgA antibodies for preventing mucosal carriage and transmission of SARS-CoV-2

2021 ◽  
Author(s):  
Kathrin Göritzer ◽  
Elisabetta Groppelli ◽  
Clemens Grünwald-Gruber ◽  
Rudolf Figl ◽  
Fengfeng Ni ◽  
...  
Keyword(s):  
Secretory Iga ◽  
Antigen Binding ◽  
Binding Affinities ◽  
Igg Antibody ◽  
Block Transmission ◽  
Valuable Adjunct ◽  
Iga Antibodies ◽  
Severe Infections ◽  
Mucosal Secretions

Abstract Passive delivery of antibodies to mucosal sites might be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. However, monoclonal IgG antibody therapies, currently used for treatment of severe infections, are unlikely to prove useful in mucosal sites where SARS-CoV-2 resides and replicates in early infection. Here, we investigated the feasibility of producing neutralising monoclonal IgA antibodies against SARS-COV-2. We identified two class-switched mAbs that express well as monomeric and secretory IgA variants with retained antigen binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralisation activities than IgG mAbs and were able to reduce SARS-CoV-2 infection in an in vivo murine model. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

scholarly journals Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients

2020 ◽  
Author(s):  
Zixian Zhao ◽  
Yu Zhao ◽  
Yueqing Zhou ◽  
Xiaofan Wang ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Time Course ◽  
Single Cell Analysis ◽  
Lung Damage ◽  
Mouse Lung ◽  
Epithelial Barrier ◽  
Epithelial Barriers ◽  
Lung Progenitor

AbstractThe high mortality of severe 2019 novel coronavirus disease (COVID-19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary edema and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process1. Here by analyzing the bronchoalveolar lavage fluid (BALF) of COVID-19 patients through single cell RNA-sequencing (scRNA-Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re-establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell-derived cell population into damaged mouse lung. Time-course single-cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long-term engrafted into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID-19 patients with massive leukocyte infiltration. Altogether this work uncovered the mechanism that how various lung progenitor cells work in concert to prevent and replenish alveoli loss post severe SARS-CoV-2 infection.

scholarly journals E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

2018 ◽  
Vol 115 (7) ◽  
pp. E1560-E1569 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Sung-Hyun Park ◽  
Mao-wen Weng ◽  
Hsiang-Tsui Wang ◽  
William C. Huang ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Human Lung ◽  
Mouse Lung ◽  
Urothelial Cells ◽  
Bronchial Epithelial ◽  
Murine Lung ◽  
Repair Activity ◽  
Tumorigenic Transformation ◽  
Bladder Cells

E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2-propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.

scholarly journals Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency

2006 ◽  
Vol 80 (1) ◽  
pp. 192-200 ◽  
Author(s):  
Ashley L. Steed ◽  
Erik S. Barton ◽  
Scott A. Tibbetts ◽  
Daniel L. Popkin ◽  
Mary L. Lutzke ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Viral Gene Expression ◽  
Gamma Interferon ◽  
Viral Gene ◽  
Herpesvirus Infection ◽  
Murine Gammaherpesvirus ◽  
Ifn Γ ◽  
Gammaherpesvirus 68 ◽  
Novel Strategy

ABSTRACT Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-γ) or the IFN-γ receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (γHV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-γ is a powerful inhibitor of reactivation of γHV68 from latency in tissue culture. In vivo, IFN-γ controls viral gene expression during latency. Importantly, depletion of IFN-γ in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-γ is important for immune surveillance that limits reactivation of γHV68 from latency.

Flagellin induces innate immune genes in bronchial epithelial cells in vivo: Role of TET2

2021 ◽  
Author(s):  
Wanhai Qin ◽  
Xanthe Brands ◽  
Cornelis Veer ◽  
Alex F. Vos ◽  
Brendon P. Scicluna ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Bronchial Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

scholarly journals Tissue factor–bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo

2012 ◽  
Vol 130 (6) ◽  
pp. 1375-1383 ◽  
Author(s):  
Jin-Ah Park ◽  
Asma S. Sharif ◽  
Daniel J. Tschumperlin ◽  
Laurie Lau ◽  
Rachel Limbrey ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tissue Factor ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial

scholarly journals A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5463-5472 ◽  
Author(s):  
Davide Bagnara ◽  
Matthew S. Kaufman ◽  
Carlo Calissano ◽  
Sonia Marsilio ◽  
Piers E. M. Patten ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
Adoptive Transfer ◽  
Severe Combined Immunodeficiency ◽  
Immune Surveillance ◽  
Lymphocytic Leukemia ◽  
Unknown Etiology ◽  
Lymphoid Tissues ◽  
Transfer Model

AbstractChronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity.

scholarly journals In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells.

1992 ◽  
Vol 116 (1) ◽  
pp. 167-176 ◽  
Author(s):  
D Wren ◽  
G Wolswijk ◽  
M Noble
Keyword(s):  
Adult Life ◽  
Cell Types ◽  
Adult Rats ◽  
Optic Nerves ◽  
Limited Life ◽  
Old Rats ◽  
Vitro Analysis

We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes. In addition, the O-2Aperinatal progenitor population appears to have a limited life-span in vivo, while O-2Aadult progenitors appear to be maintained throughout life. O-2Aperinatal progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2Aadult progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions: (a) From what source do O-2Aadult progenitors originate; and (b) how is the O-2Aadult progenitor population maintained in the nerve throughout life? We now provide in vitro evidence indicating that O-2Aadult progenitors are derived directly from a subpopulation of O-2Aperinatal progenitors. We also provide evidence indicating that O-2Aadult progenitors are capable of prolonged self renewal in vitro. In addition, our data suggests that the in vitro generation of oligodendrocytes from O-2Aadult progenitors occurs primarily through asymmetric division and differentiation, in contrast with the self-extinguishing pattern of symmetric division and differentiation displayed by O-2Aperinatal progenitors in vitro. We suggest that O-2Aadult progenitors express at least some properties of stem cells and thus may be able to support the generation of both differentiated progeny cells as well as their own continued replenishment throughout adult life.

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