bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhinovirus infection modulates MHC class I-related chain A and B molecules in human respiratory epithelial cells (133.37)
Authors: Stanciu Luminita A , Rushwan Nagla , Telcian Aurica G , Johnston Sebastian L 
Published: January 2023

Abstract
Cell surface and soluble MICA and MICB molecules induced by stress/viruses could activate, respectively impair, cytotoxic activity of NKG2D+ NK and CD8 T cells.
We hypothesised that rhinovirus (RV) infection of bronchial epithelial cells alters the balance between activatory (surface) and inhibitory (soluble) MICA and MICB molecule.
MIC molecules were investigated in BEAS-2B cells (a bronchial epithelial cell line) exposed in vitro to RV1B MOI 1 ± IL-4 10ng/ml up to 72 hours by flow cytometry (intracellular and cell surface) and ELISA (soluble molecules in supernatants).
RV1B infection of BEAS-2B cells increased the levels of surface MICA in a dose- and replication-dependent manner, peaking at 24h and gradually decreased during 72h. RV1B-induced soluble MICA molecule levels increased in a time-dependent manner, peaking at 72h. IL-4 presence during RV1B infection increased RV1B-iduced surface MICA (MFI: 72±9 versus 45±10, p&lt;0.05) and soluble MICA levels (12±8 versus 9±7, p=0.3).
Intracellular and surface MICB molecules were decreased by RV1B infection and IL-4 further decreased intracellular levels.
To conclude, RV1B infection in BEAS-2B cells in the presence of IL-4 up-regulated the surface MICA levels but also increased soluble MICA levels which could inhibit in vivo the activation of NKG2D+ cells and by doing this delaying virus clearance and prolonging the airway inflammation in virus-induced asthma.
Calpain-dependent degradation of transcription factors and X-linked inhibitor of apoptosis (XIAP) in colon epithelial cells during cell death induced by Entamoeba histolytica (133.4)
Authors: Kim Kyeong Ah , Shin Myeong Heon , Lee Young Ah 
Published: January 2023

Abstract
Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in human beings. During the infection in the colonic tissues, amoebic trophozoites have a capability to kill host cells via apoptosis or necrosis, which triggers IL-8-mediated acute inflammatory responses. However, signaling pathways involved in host cell death by E. histolytica is not fully defined. In this study, we examined whether calpain is closely involved in cleavage of transcription factors and XIAP, which are responsible for cell survival, during cell death of colon epithelial cells induced by live trophozoites of E. histolytica. Incubation with amoebic trophozoites induced PS externalization in CaCo2 cells in a time and dose-dependent manner. In addition, E. histolytica activated m-calpain and caspase-3 in CaCo2 cells. Moreover, incubation with amoeba resulted in marked degradation of STAT proteins (STAT1, 2, 3, 5, and 6), NF-¿B (p65 or p50), and XIAP in CaCo2 cells. However, I¿B, an inhibitor of NF-¿B, was not cleaved in CoCo2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins, NF-kB, and XIAP was inhibited by pretreatment of cells with a cell permeable calpain inhibitor, calpeptin. Furthermore, calpeptin, but not z-VAD-fmk, reduced Entamoeba-induced DNA fragmentation in CoCo2 cells. These results suggest that calpain-mediated degradation of anti-apoptotic proteins, such as transcription factors and XIAP, is required for acceleration of cell death in colon epithelial cells induced by Entamoeba histolytica.
Influenza A Virus Infects Human Mast Cells and Increases Expression of Antiviral Genes (133.43)
Authors: Marcet Candy , St. Laurent Chris , Singh Nav , Befus A. Dean 
Published: January 2023

Abstract
Evidence is building for the role of mast cells (MC) in innate immune responses against various pathogens. In the lungs, MC exist close to epithelial cells (EC), where influenza A virus (FluA) primarily replicates. Viruses such as dengue virus and HIV are capable of replicating in MC, but no report of FluA replication in MC currently exists. Our aim was to characterize FluA infection in human MC and examine host factors in MC that might regulate virus replication.
Human MC lines (HMC1 and LAD2) and primary MC cultured from human peripheral blood (PBMC) were exposed to FluA (PR/34/8, 20HAU/ml). EC lines (MDCK and Calu-3) were used as comparative cell types. The presence of RNA viral transcripts by RT-PCR followed similar time courses in MC and EC. Supernatants were harvested at various time points after infection. Total FluA parcticles as determined by ability to agglutinate red blood cells was significantly lower (p&lt;0.05) in MC (27 ± 13 HAU/ml) than in EC (480 ± 160 HAU/ml) at 4 days after infection. Infectious FluA particles as determined by ability of supernatants to infect Calu-3 were detected from EC but not MC.
Since FluA replication was diminished in MC compared to EC, we explored whether MC express and/or upregulate antiviral genes in response to FluA. We have data that RNA transcripts of antiviral genes, such as nitric oxide synthase 3 and protein kinase R, are increased in MC exposed to FluA. Our evidence suggests that MC have antiviral mechanisms to restrict FluA replication, which may contribute to host immunity.
Geriatric adults have a significant defect in interferon-alpha production in response to influenza (133.50)
Authors: Canaday David H , Amponsah Naa Ayele , Ramachandra Lakshmi 
Published: January 2023

Abstract
Ninety percent of deaths attributed to influenza are in the elderly. While age-related decline in T cell function has been demonstrated, much less is known about the innate immune responses during natural infection and vaccination that shape humoral and cell mediated responses.
We analyzed interferon alpha (IFN-alpha) production in peripheral blood mononuclear cells (PBMCs) isolated from younger adult and geriatric individuals that were stimulated with influenza or TLR ligands. A majority of geriatric PBMCs made significantly lower amounts of IFN-alpha, a signature anti-viral cytokine, in response to influenza. Surprisingly, geriatric PBMCs had normal production of IFN-alpha in response to the TLR9 ligand, CpG ODN, and the TLR7 ligand, guardiquimod. We determined that plasmacytoid dendritic cells (pDCs) are the main producers of IFN-alpha in response to influenza, CpG ODN and guardiquimod in PBMCs by cell depletion studies, and that influenza signals through TLR7. We are currently investigating the mechanism for this defect in IFN-alpha production in response to influenza by geriatric pDCs.
A better understanding of the specific innate immune responses to influenza in geriatric individuals may allow a better understanding of the pathophysiology of the host-influenza interaction and therefore allow a more targeted approach to vaccine design.
This work is supported by AI077056 and AI36219.
Structure and function of the activating receptor CLEC-2. (134.10)
Authors: O'Callaghan Chris A , Watson Aleksandra A , Fenton-May Angharad E , Christou Charita M 
Published: January 2023

Abstract
We are studying the immune recognition of diseased or damaged cells. In cytotoxic cells, the C-type lectin-like receptor NKG2D plays a key role in this distinction. A number of related receptors are expressed on immune cells and we are studying their function. CLEC-2 is an activating receptor which is also expressed on platelets. We have crystallized CLEC-2 and solved its structure. We have used recombinant CLEC-2 as a probe to identify an endogenous ligand for CLEC-2, which is known as podoplanin. The podoplanin-CLEC-2 interaction triggers an activating signal in the cell expressing CLEC-2. We have also solved the crystal structure of rhodocytin, an exogenous ligand for CLEC-2. The structures of both ligand and receptor allow us to produce molecular models of the interactions and its effects. These suggest that the ligand-receptor interactions will cluster CLEC-2 on the cell surface. We have used surface plasmon resonance to define the binding characteristics of the interactions of CLEC-2 with both its exogenous and endogenous ligands.
Control of NK cell activation by distribution and mobility of ligands on target cells (134.16)
Authors: Gross Catharina C , Martinez Emily , Long Eric O. 
Published: January 2023

Abstract
Natural killer (NK) cells are large granular lymphocytes that comprise 5-15% of peripheral blood mononuclear cells and function through cytokine production or cytotoxicity. The response of NK cells to contact with other cells is regulated through many different receptor-ligand interactions. However, it is not clear yet to what extent the distribution and mobility of ligands anchored into the plasma membrane of target cells influence NK cell activation and immune synapse formation during NK-target cell interactions. To study the role of the distribution and mobility of ligands on target cells, and to avoid the use of toxic inhibitors such as cyclodextrin, cholesterol-auxotroph Drosophila cell line S2 was transfected with GPI-linked CD48 (the ligand of NK cell receptor 2B4) and ULBP1 (the ligand of NK cell receptor NKG2D) and grown in serum-free conditions to eliminate cholesterol-enriched domains. 2B4- and NKG2D-dependent activation of NK cells was altered when the ligands where expressed in cholesterol-free S2 cells, suggesting a role of target cell membrane micro-domains in the response of NK cells. Experiments are underway to test how the mobility of ligands on the target cell may influence recognition by NK cells.
The chemokine receptor CxCR3 retains invariant natural killer T cells in the thymus (134.21)
Authors: Elewaut Dirk , Franki Ann Sophie , Dewint Pieter , Lane Thomas , Deforce Dieter , Drennan Michael 
Published: January 2023

Abstract
Invariant Natural Killer T (iNKT) cells are characterized by expression of a semi-invariant Vα14-Jα18 TCRα chain and NK lineage markers such as NK1.1. In the thymus, iNKT cell maturation coincides with NK1.1 up-regulation and paradoxically, the retention of the mature NK1.1+ subset. The signals involved in the retention of iNKT cells remain undefined. Here, we report that upregulation of the chemokine receptor CxCR3 on thymic iNKT cells serves to retain them in the thymus of adult mice. Strikingly, genetic deletion or neutralization of CxCR3 results in leakage of thymic iNKT cells into the peripheral circulation. These results suggest an unexpected role for CxCR3 in thymic iNKT cell homing and localization patterns.
Murine B-1 B lymphocytes have active phagocytic and microbicidal abilities (134.31)
Authors: Li Wei , Gao Jixin , Ma Xiaoying , Gu Weijie , Zhang Ke , Liu Yufeng 
Published: January 2023

Abstract
It has long been recognized that B cells lack phagocytic capabilities. Until recently, B cells from teleost fish were shown to have potent phagocytic abilities for particle antigens; however, whether mammalian B cells are able to accomplish phagocytosis is still not clear. Here we demonstrated that mouse peritoneal cavity (PerC) B-1 B cells, which are thought to be the counterpart of the teleost fish blood B cells, had in vivo and in vitro phagocytic activities to Staphylococcus aureus and polystyrene fluorescent microspheres. Ingestion of particles by B cells led to activation of degradative pathways, resulting in phagolysosome formation and intracellular killing of ingested microbes. About 10% of PerC B cells, mostly CD11b+ B-1 B cells, showed phagocytic activities, and there was no apparent difference between B-1a and B-1b cells in the capabilities for phagocytotisis. Spleen B cells showed a very low degree of phagocytosis. Our results revealed for the first time that mammalian B-1 B cells have phagocytic capacities, which may contribute to their role in innate and adaptive immunity.
Interleukin-12 p40 and p35 subunit production coincides with inverse relationship between innate and acquired immune responsiveness in mice initially dosed with cationic lipid DNA complexes (JVRS-100) (134.42)
Authors: Vaughn Marla Lay , Callejo Bernadette , Liang Lily , Fairman Jeffery 
Published: January 2023

Abstract
Closely spaced intravenous (IV) administration of a potent activator of innate immunity, cationic lipid DNA complexes (JVRS-100), induces a short (7-10) day refractory period during which re-treatment with the drug is associated with reduced innate immune activation measured by decreased circulating interferon-? levels compared to primary treatment. Since innate immune responses are thought to upregulate adaptive immune response and we observed a reduction, it was surprising to find that IV administration of JVRS-100 one day prior to a single influenza vaccine dose significantly enhanced the influenza-specific antibody response. Adoptive transfer experiments were conducted to dissect the mediator of this effect. Interferon-? response to JVRS-100 stimulation was reduced after transfer of 3 hour post treatment serum and 3 or 6 hour post treatment splenocytes. In contrast transfer of 6 hour post treatment serum resulted in a significantly increased interferon-? response to repeat immune stimulation. In addition adoptive transfer of 6 hour, but not 3 hour, post-treatment splenocytes conferred a vaccine enhancement nearly equivalent to that seen after IV pre-treatment. Cytokine studies of post treatment sera support an important role for IL12p40 and p35 subunits in these observations.
Supported by NIAID grant "Innate Immune Stimulation as a Pathogen Countermeasure"
Chronic alcohol ingestion alters zinc homeostasis along the gut-pulmonary axis and decreases bacterial clearance in the lung (134.43)
Authors: Joshi Pratibha C , Mehta Ashish , Guidot David M 
Published: January 2023

Abstract
Although it has long been recognized that alcohol abuse is associated with zinc deficiency and chronic lung infections, it is not known if these two observations are interrelated. We hypothesized that chronic alcohol abuse decreases zinc bioavailability in the alveolar space resulting in the dysfunction of alveolar macrophages and increases susceptibility to infections. Sprague-Dawley rats were fed an isocaloric liquid diet with or without alcohol for 6 wks. The expression of zinc transporters and zinc storage protein metallothionein (MT) was examined in small intestine and alveolar macrophages from control- and alcohol-fed rats. In some experiments, rats were inoculated with Klebsiella pneumoniae intratracheally and after 24h, bacterial burden in the lung was determined by quantifying the number of colony forming units (CFUs). The expression of zinc transporters ZIP4, ZIP1, ZNT1 and MT was significantly decreased in the small intestine of alcohol-fed rats. Zinc concentration of alveolar macrophages and bronchoalveolar lavage fluid, and the expression of ZIP4, ZIP1, ZNT1, and MT were significantly reduced in the macrophages from alcohol-fed rats. In addition, the alcohol-fed rats showed a decrease in the bacterial clearance (significantly higher CFUs/lung) as compared to the control-fed rats. These data suggest that chronic alcohol ingestion decreases zinc status of the gut resulting in the decreased bioavailability of zinc in the alveolar space, alters alveolar macrophage immune function, and decreases bacterial clearance in the lung.
Supported by P50 AA013757 and 2R01 AA011660-05A1
Live Imaging of Cytotoxic Immune Synapses Reveals LFA-1-dependent Ligand Distribution and Bidirectional Vesicular Traffic (134.5)
Authors: LIU DONGFANG , Bryceson Yenan T. , Meckel Tobias , Vasiliver Gaia , Dustin Michael L , Long Eric O 
Published: January 2023

Abstract
Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To obtain information on the dynamics and control of cytotoxic immune synapses we imaged primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors by total internal reflection fluorescence microscopy. In the presence of the LFA-1 ligand ICAM-1, ligands of co-activation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Exocytosed lysosomal protein LAMP-1 accumulated in a central and stable region of the synapse, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. In the absence of ICAM-1, the distribution of receptor ligands, of exocytosed LAMP-1, and of lysosomal compartment contacts with the plasma membrane was dispersed. Thus, live imaging has revealed LFA-1-dependent organization of cytotoxic immune synapses, including a central region of bidirectional vesicular traffic.
Role of IL-17 in the mucosal adjuvant activity of cholera toxin for epicutaneous vaccines (134.53)
Authors: Boyaka Prosper N , Iwakura Yoichiro , Chaplin David D 
Published: January 2023

Abstract
It is now established that the mucosal adjuvant activity of cholera toxin (CT) involves the induction of IL-1 and other proinflammatory cytokines. Interleukin-17 (IL-17) is a cytokine implicated in the regulation of inflammation. In addition, Th-17 associated cytokines TGF-beta and IL-6 act as Ab mu to alpha class switch factor and promote the terminal differentiation of B cells into plasma cells, respectively. We examined the role played by IL-17 in the mucosal adjuvant activity of CT for epicutaneous vaccines. Groups of IL-17 KO and control C57BL/6 mice were immunized by epicutaneous application of 50 micrograms of CT with 1 mg ovalbumin (OVA). Control mice developed high levels of OVA- and CT-specific IgA Abs in the serum, and in fecal extracts. The adjuvant activity of CT in control mice also resulted in high antigen-specific IgG responses in the serum with a profile of IgG subclasses characterized by a IgG1&gt;IgG2a. The IL-17 KO mice given the same epicutaneous vaccine exhibited enhanced serum and fecal IgA responses. On the other hand, serum IgG responses were of the same magnitude and profile than control littermates, suggesting that IL-17 signaling affects CT-induced IgA but not IgG Abs.
Anaphylatoxin Signaling in Murine Glial Cells (134.58)
Authors: Ingersoll Sarah A , Martin Carol B , Martin Brian K 
Published: January 2023

Abstract
Autoimmune destruction of myelin in diseases of the CNS is known to involve several immune effector mechanisms, including complement. The brain is considered an immunoprivileged site and is protected by the blood brain barrier; however, it has been shown that complement proteins are produced locally by glial cells. It has been found that glia express receptors for anaphylatoxins, C3a and C5a. Currently, our lab is investigating the effect of anaphylatoxins on glial cell activation as well as their overall role in demyelination and remyelination pathology. To study the role of anaphylatoxins in vitro, our lab created novel adenoviral vectors to express murine C3a or C5a. To study the role of anaphylatoxin signaling in glia we treated murine astrocyte and microglial cells with C3a, C5a or both anaphylatoxins, then examined various downstream effects. Using Western blots, we found that MAPK pathway proteins, ERK1/2, were highly phosphorylated when microglia were stimulated with C5a, but not C3a. In contrast, ERK1/2 were not activated in astrocytes treated with either anaphylatoxin. Finally, C5a was able to induce chemtoaxis in J774 murine macrophages; however we did not see significant migration of primary astrocytes or BV-2 microglia. These studies suggest that anaphylatoxin signaling and/or the functional consequences of that signaling is differentially regulated in a cell-specific manner.
Complement C5 deficiency in inbred mouse strains (134.61)
Authors: Lake Jeffrey 
Published: January 2023

Abstract
The Jackson Laboratory repository (JAX) serves as a centralized facility to import, develop, preserve, and distribute mouse models to the scientific community. Approximately 300 strains are added annually to one of the largest collection of characterized mouse strains available. JAX currently has 194 inbred mouse strains; 103 strains are maintained in living colonies and 91 strains are cryopreserved. Selecting appropriate inbred strains for study may be difficult requiring careful selection. For example, at least 14 inbred strains and many of the BXD recombinant inbred strains have a deficiency of the fifth complement component, C5. Mice deficient in C5 are more susceptible to a variety of infectious diseases. C5 also plays an important role in autoimmune diseases, allergic airway disease, and in various other biological processes. Other factors for model selection of inbred strain selection include strain background including breeding performance, MHC haplotype, other known mutations, and other associated phenotypes. Supported by NCRR (RR09781, RR11083, RR16049), NIA, HHMI, and donations from several private foundations
Structure-function analysis of gC1qR/p33 using deletion mutants show additional binding sites for C1q. (134.69)
Authors: Xu Sulan , Menzies Catherine A , Vinayagasundaram Rama , Mathew Sally , Vinayagasundaram Uma , Peerschke Ellinor I.B , Jesty Jolyon 
Published: January 2023

Abstract
Surface expressed or soluble gC1qR has been shown to activate complement and to play a role in various inflammatory processes. By peptide mapping and antibody inhibition studies, we had previously identified a binding site for C1q in a gC1qR domain contained within residues 76-93. However, although mAbs 60.11, which recognizes residues 76-93, can inhibit C1q binding to gC1qR, the inhibition is not complete. Similarly, binding of C1q to a truncated form of gC1qR lacking residues 76-93 is reduced by only 40-50% when compared to the full-length gC1qR. These findings therefore prompted us to look for additional binding sites elsewhere in the molecule. To this end, we generated several recombinant gC1qR proteins by deletion of domains of very high negative charge— and which, based on their location in the crystal structure—were predicted to interact with solution-phase ligands. The capabilities of these mutants to bind to C1q were therefore examined by comparing to the binding of the full-length gC1qR. Analyses of the data reveal the presence of two additional binding sites for C1q—one contained within residues 190-192 and another within residues 144-162. These results not only demonstrate well the value of crystal-based structure-function predictions, but also allow the identification of potential targets for drug design to alleviate complement-mediated inflammation. [Supported by NIH-NIAID Grant R01 AI-060866]
Plasma lipoproteins are important components of the host defense system? (134.74)
Authors: Han Runlin 
Published: January 2023

Abstract
Plasma lipoproteins [VLDL, LDL, and HDL] function primarily in lipid transport among tissues and organs. However, the cumulative evidence may support that as part of innate immunity, lipoproteins may also broadly prevent or inhibit bacterial, viral and parasitic infections. Lipoproteins can detoxify lipopolysaccharide and lipoteichoic acid. Lipoproteins neutralize a vast of enveloped and non-enveloped DNA and RNA viruses. Staphylococcus aureus α-toxin is bound and inactivated by purified LDL. LDL also directly binds to some bacteria, but the pathophysiological significance of these LDL-pathogen interactions remains to be elucidated. The oxidized LDL (ox-LDL), which can be induced by infections, has several anti-infective activities. It protects against endotoxin-induced tissue damage. The antibody against phosphorylcholine (PC) elicited by ox-LDL may provide a broad protection against pathogens since PC has been detected on a number of prokaryotes and many nematodes; Ox-LDL-activated macrophages enhance phagocytosis of pathogens. Thus, the oxidation of LDL may be an important response of host against infections. Importantly, Lipoprotein(a) might inhibit the binding of a number of pathogens to plasminogen, subsequently protect against the invasion of pathogens. Taken together, it might be reasonable to introduce the anti-infective role of plasma lipoproteins into immunology textbooks.