bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of IL-19 Expression by IL-13 and IL-17A in Human Airway Epithelium (B114)
Authors: Huang Fei , Thai Philip , Wachi Shinichiro , Wu Reen 
Published: January 2023

Abstract
Increasing evidences have shown that IL-19 is up-regulated in chronic inflammatory diseases, such as psoriasis, and asthma. Its significance is further highlighted for its ability to enhance Th2 cytokines expression in T cells, and inflammatory cytokines in monocytes. We have recently found that IL-17A and IL-13 are able to stimulate the expression of IL-19 secretion in both primary airway epithelium and human bronchial epithelium-1 (HBE1) cell line. Additionally, IL-17A, a proinflammatory cytokine which is crucial to many autoimmune diseases and bacterial infection, and IL-13, a Th2 cytokine which is predominated in allergic responses, can synergistically stimulate IL-19 expression. A similar synergism on IL-19 stimulation was observed when cells were treated with IL-4 and IL-17A. The synergism was not observed when IL-17A was co-treated with other proinflammatory, Th1, or immunosuppressive cytokines, such as TNF-α, IL-2, IFN-gamma, IL-10, etc. The increased expression of IL-19 is regulated by IL-13, and IL-17-induced STAT6, and NF-κB transcriptional activation respectively. In conclusion, the synergism of IL-13 and IL-17 on IL-19 production highly suggested that the airway mucosal immunity is regulated through an IL-13/IL-17A/IL-19 /Th2 cytokine axis. This axis needs to be further characterized and verified in allergic/Th2 dysregulated diseases.
Evualation of biocompatibility of epoxy resin-based, zinc oxide eugenol-based, calcium hydroxide-based root canal sealers by in situ proinflammatory cytokine production. (B118)
Authors: SOLIS-SOTO JUAN MANUEL , QUINTANILLA-RODRIGUEZ LIZETH EDITH 
Published: January 2023

Abstract
Histopathological studies have demonstrated that root canal sealers induce mild to severe inflammatory reactions. Proinflammatory cytokines are one of the main causative agents of inflammation. In situ production of these cytokines can be an indicative of citotoxicity. In the present work it is studied the in situ expression of proinflammatory cytokines as a biocompatibility marker for dental sealers of different composition. After inoculating the dorsal dermis of CD-1 mice with AH Plus (epoxy resin based), Tubliseal (Zinc-oxide eugenol based) and Sealapex (calcium hydroxide based), the tissue was prepared for immunocytochemical studies to analyze presence of IL-1beta, IL-6, IL-12, TNF-alpha and Interferon-gamma. AH Plus induced the strongest reaction (p&lt;0.01), mainly in the acute inflammation, with immunoreactivity to IL-1beta, TNF-alpha and IL-12 in several cells in the inflammatory tissue and in the dermis. Few cells of the epidermis were immunoreactive to IL-1beta. No significative difference was found in the amount of immunoreactive cells after inoculation with Tubliseal and Sealapex (p&lt;0.05), only a few cells were immunoreactive to IL-12, IL-1beta and TNF-alpha. Proinflammatory cytokines are an important key in the pathogenesis of the inflammation caused by root canal sealers. Calcium hydroxide based dental sealers showed better in situ biocompatibility.
This work was supported by grants from PROMEP (SEP) 103.5/05/2485 and PAICYT SA1420-06 (UANL).
Neonatal influenza infection induces persistent airway dysfunction (B119)
Authors: Cormier Stephania , You Dahui , Ripple Michael , Simms Tiffany 
Published: January 2023

Abstract
Infection with respiratory syncytial virus (RSV) and influenza is common during infancy. Interestingly, neonatal infection with RSV predisposes to persistent airway hyperreactivity (AHR), pulmonary inflammation, and Th2-skewed immune responses upon reinfection as an adult. A major difference in the host immune response to infection with influenza (Th1 dominant response) and RSV (Th2 response) exists. The present research sought to determine whether neonatal infection with a strong Th1 immune stimulator, such as influenza, could elicit an initial Th1 response and what the subsequent response to reinfection would be. Seven day old mice were infected with influenza (H1N1, 100 TCID50/mouse) or RSV (10e6 TCID50/mouse). Bronchoalveolar lavage fluid (BALF) was isolated to measure cytokines and cellularity at 10 d.p.i. (H1N1) or 6 d.p.i. (RSV). Pulmonary function, lung histology, and BALF cellularity and cytokine production were measured in adult mice (10–12 wks). In the acute phase of infection, H1N1 caused a Th1 response in the lung, characterized by INF-g production and neutrophil recruitment; while RSV led to a Th2 response characterized by IL-13 production. Both viruses elicited unresolved lung dysfunction and pulmonary inflammation characterized by elevations in alveolar macrophages. These data highlight the importance of delaying respiratory viral infections until the immune system matures.
This publication was made possible by NIH grant number P20 RR020159 from the LSU/Tulane COBRE-CEIDR Program of the National Center for Research Resources. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH.
Activated CD8 T cells can stimulate CD4 T cells by direct interaction (B12)
Authors: Romagnoli Pablo Alberto , Altman John D 
Published: January 2023

Abstract
Protective immunity against viruses is characterized by the generation of effective CD8 T cell memory in the presence of helper CD4 T cells. CD4 T cells impact in the programming of CD8 T cells by licensing antigen presenting cells (APCs) involved in priming. It is also known that CD4 T cells are necessary for activated CD8 T cells to differentiate into memory. However, it is not well understood how help is delivered at this second stage due to:
low probability of having CD4, CD8 T cells and APCs together; andabsence of accepted models where CD4 interact directly with CD8 T cells.
Here we propose a model of CD8:CD4 interaction where MHC class II molecules, transferred onto CD8 T cells by trogocytosis, are able to present antigen directly to CD4 T cells. Our results show that only antigen-specific CD8 T cells received MHC class II molecules transfer from APCs . These MHC class II positive activated CD8 T cells are able to prime naïve and restimulate experienced CD4 T cells to release great amounts of helper cytokines like IL2, IFNγ and TNFα and induce proliferation of antigen specific CD4 T cells in vivo.
These observations suggest a novel functional interaction between CD8 and CD4 T cells that might explain how help is delivered in the differentiation phase of memory CD8 T cells. Furthermore, this model would not only contemplate the occurrence of direct CD4 T cell help for CD8 T cells, but also the possiblity of an interface for immune regulation depending on the profile of CD4 T cells contacting the activated CD8 T cell.
Support for this Research comes from the National Institutes of Health, Grant: 1RO1AI042373-04, PI: John D. Altman.
Cellular neuropathologic effects of hemozoin, a toxin produced by Plasmodium falciparum, the causative agent of human malaria (B121)
Authors: Martiney James A , Harkins Caroline , Berman Joan W , Eugenin Eliseo A 
Published: January 2023

Abstract
Malaria, caused by an intracellular protozoan parasite of the genus Plasmodium, is responsible for 2–3 million deaths and 300–500 acute illnesses annually. A major morbidity factor is cerebral malaria, characterized by enhanced blood-brain barrier permeability, leukocyte infiltration and/or activation, and neuronal dropout. The pathogenesis of cerebral malaria remains unknown. Hemozoin, a by-product of intraerythrocytic parasite mediated hemoglobin catabolism, is released when the parasite lyses the host erythrocyte. This potential toxin is found in the brain parenchyma of cerebral malaria cases. The effects, if any, of hemozoin on human brain cells has not been studied in detail. Our data demonstrates that astrocytes actively phagocytize hemozoin, resulting in a time and concentration dependent toxicity and loss of viability. Further analysis demonstrated a secondary loss of neurons in astrocyte-neuron co-cultures. Morphologic characteristics of apoptosis such as membrane blebbing were observed in astrocytes exposed to hemozoin. Apoptosis was subsequently corroborated via Western blot analyses and TUNEL confocal microscopy. Taken together, our results suggests that hemozoin can induce significant pathogenic responses in CNS cells that can contribute to the development of cerebral malaria.
This work was supported by the NIH Centers for AIDS Research Grant AI-051519 and particularly by a KO1 grant from the National Institute of Mental Health to E.A.E. (MH076679).
Diverse and Distinctive Dendritic Cell Subtypes in the Respiratory Tract (B129)
Authors: Kim Taeg S , Braciale Thomas J 
Published: January 2023

Abstract
Dendritic cells (DCs), relatively rare subpopulations of cells widely distributed in organized lymphoid organs and periphery tissues, represent the most efficient antigen presenting cells capable of inducing robust pathogen-specific CD8+ and CD4+ T immunity in vivo. Upon pulmonary microbial infections, DCs residing in the respiratory tract (RDCs) acquire pathogen-derived Ags in the lung, leave the organ and enter the regional lymph nodes. The emigrated RDCs take a critical part in the induction of an adaptive cellular immune response. However, the nature of migratory RDCs is poorly understood, which is in part due to a tenuous characterization of RDC subtypes. We combined phenotypic analysis with functional assays to define a cellular composition of DCs in the respiratory tract of naïve mice. In the ends, we defined at least six subpopulations of CD11c+ cells including alveolar macrophages. Among the RDC subtypes, CD103+ and CD11b med-hi MHC II hi DC subsets feature greater CD86 expression and phagocytic/pinocytic activity than the rest. Our study shows the complexity of DC network in the respiratory tract, implying that the diverse subtypes of RDC may display a specialized role in establishing a protective host immune response upon pulmonary infection. Future study aims at probing a functional specialization among RDC subtypes in a respiratory viral infection model.
Supported by USPHS Grants AI-15608, HL-33391, AI-37293.
Endothelial cell apoptosis induced by Dengue virus (B133)
Authors: Yen Yu-Ting , Chen Hsuen-Chin , Lin Yang-Ding , Wu-Hsieh Betty 
Published: January 2023

Abstract
Vascular leakage and hemorrhagic diathesis are life-threatening complications that occur to dengue hemorrhagic patients. However, the pathogenic mechanism of hemorrhage is not well understood. It has been shown that endothelial cells are permissive to dengue virus (DV) infection in vitro and DV antigen is found in endothelial cells of autopsy specimens collected from patients who died of DHF. Therefore, the study of interaction between DV and endothelial cells will shed light on the mechanism of dengue hemorrhage.
We established a dengue hemorrhage mouse model in immunocompetent C57BL/6 mice by injecting DV serotype 2 strain 16681 intradermally. While high dose DV inoculation induced hemorrhage in all of the mice, 1/3 of those injected with 4–8 x 107 PFU developed hemorrhage in the subcutaneous tissues by day 3 of infection. Importantly, hemorrhage was accompanied by severe thrombocytopenia and vascular leakage. Double immunofluorescence staining revealed that DV targeted both macrophages and endothelial cells in the subcutaneous tissues. In vitro studies showed that human umbilical cord vein endothelial cells (HUVEC) and microvascular endothelial cell line (HMEC) were susceptible to DV and TNF-α enhanced DV-induced apoptosis. In addition, DV infection induced endothelial cell NOS and ROS production and endothelial cell apoptosis, which were also enhanced by TNF-α. These findings demonstrate that dengue virus and TNF-α-induced endothelial cell apoptosis is mediated by ROS and NO.
Interleukin-15: Multiple roles in controlling HIV infection in chimpanzees (B143)
Authors: Rodriguez Annette Rose , Hodara Vida L , Morrow LaShayla , Sanchez Melissa , Knudsvig Tracey , Murthy Krishna K 
Published: January 2023

Abstract
We have recently shown that Interleukin-15 (IL-15) plays a crucial role in eliciting interferon-gamma (IFN-γ) production from CD3−CD8+ NK cells in HIV infected chimpanzees (Pan troglodytes). CD3−CD8+ IFN-γ+ NK cells were consistently higher than CD3+CD8+ IFN-γ+ T cells and CD3−CD56+ IFN-γ+ NK cells by flow cytometry analysis. Accordingly, these findings prompted further investigation into the role of IL-15 during HIV infection. Analysis of fresh chimpanzee leukocytes revealed that a rare subpopulation of T cells express surface IL-15. HIV infected chimpanzees were shown express surface IL-15 on &lt; 1 % to 3 % of T cells. Multiparameter flow cytometry analysis utilizing a whole blood system demonstrated that the cells were CD3+CD4+CD16+IL15+ and CD3+CD8+CD16+IL15+ T cells. These populations were shown to be CD25 negative, however, in vitro stimulation of PBMCs with interleukin-15 resulted in upregulation CD4+CD25+ T cells. Additional blood specimens from HIV infected chimpanzees examined during routine physicals also exhibited CD3−CD8+ IFN-γ+ NK cells &gt; CD3+CD8+ IFN-γ+ T cells (p&lt; 0.009, n=10). Research has shown that CD8+ lymphocytes play a substantial role in controlling HIV replication and declining CD4 cells leads to an increase in susceptibility to pathogens. During this study IL-15 was also shown to induce IFN-γ and TNF-α expression from this CD3−CD8+ NK cells. These findings provide additional insights on the influence of IL-15 and chimpanzee resistance mechanisms during HIV infection.
Ablation of Cbl-b Provides Protection Against Transplanted and Spontaneous Tumors (B146)
Authors: Chiang Jeffrey Y. , Jang Ihn Kyung , Hodes Richard , Gu Hua 
Published: January 2023

Abstract
A significant challenge to efforts aimed at inducing effective anti-tumor immune response is that CD8+ T cells, which play a prominent role in these responses, may be unable to respond to tumors that lack costimulatory signals and that are protected by an immune suppressive environment such as that mediated by TGF-β produced by tumor cells themselves or by infiltrating regulatory T cells (Treg), often resulting in tolerance or anergy of tumor-specific T cells. Here, we show that the in vitro activation of Cbl-b-deficient (Cbl-b−/−) CD8+ T cells does not depend on CD28 costimulation and is resistant to TGF-β suppression. In vivo studies further demonstrate that Cbl-b−/− mice, but not wildtype controls, efficiently reject inoculated E.G7 and EL4 lymphomas that do not express B7 ligands, and that introduction of Cbl−/− mutation into tumor-prone ataxia telangiectasia mutated (ATM)-deficient mice markedly reduces the incidence of spontaneous thymic lymphomas. Immunohistological study shows that E.G7 tumors from Cbl-b−/− but not wildtype mice contain massively infiltrating CD8+ T cells. Adoptive transfer of purified Cbl-b−/− but not wildtype CD8+ T cells into E.G7 tumor-bearing mice leads to efficient eradication of established tumors. Thus, our data indicate that ablation of Cbl-b can be an efficient strategy for eliciting immune responses against both inoculated and spontaneous tumors.
aAPC immunization activates low affinity T cells for treatment of tumors (B147)
Authors: Zoso Alessia , De Santo Carmela , Marigo Ilaria , Bennet Jonathon Drew , Zanovello Paola , Schneck Jonathan P. , Bronte Vincenzo , Oelke Mathias 
Published: January 2023

Abstract
The development of effective anti-tumor immune responses is normally constrained by low affinity tumor specific CTL which are unable to eradicate the tumor. Strategies to rescue anti-tumor activity of low affinity melanoma-specific CTL in vivo might improve immunotherapy effectiveness. To boost the in vivo efficiency of low affinity CTL clone we immunized mice with artificial Antigen Presenting Cells (aAPC), made by covalent coupling of pepMHC-Ig dimer and B7.1-Ig molecules to magnetic beads, in a lung metastatic tumor model. Systemic administration of aAPC resulted in the complete tumor eradication and was associated with proliferation of adoptively transferred low affinity CTL clones. In vitro studies showed that aAPC, in contrast to tumor cells effectively stimulated cytokine release and TCR down-regulation, explaining the efficient in vivo activation of low affinity CTL. Thus, aAPC represent a novel adjuvant for cancer immunotherapy.
Rat dendritic cells induce tumor cell death via a NO-dependent pathway (B152)
Authors: NICOLAS Alexandra , CATHELIN Dominique , FRASZCZAK Jennifer , BONNOTTE Bernard 
Published: January 2023

Abstract
Dendritic cells play an essential role in anti-tumor immune response as they are powerful antigen-presenting cells for activation of specific antitumor T lymphocytes. Recently, several reports reveal that dendritic cells may also act as potent cytotoxic cells against tumor cells. We demonstrated here that LPS-activated rat bone-marrow-derived dendritic cells (BMDCs) are cytotoxic against rat, mouse and human tumor cells. These LPS-activated BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, TNF-a, and retain their T lymphocytes stimulation and phagocytic properties. The tumor cell death induced by these BMDCs involves high release of nitric oxide (NO). BMDC tumoricidal capacity is strongly reduced by NMMA, an inhibitor of the inducible NO synthase (iNOS). In addition, iNOS expression and high amounts of intracellular NO were detected in LPS-activated BMDCs cocultured in the presence of tumor cells. In line with these results, we demonstrated that intratumoral injection of LPS activates NO secretion by tumor-infiltrating DCs which impedes tumor progression.
Immunosurveillance of lung melanoma metastasis in EBI-3 deficient mice by IKDCs- induced CD8+ T cells (B154)
Authors: Sauer Kerstin Annika , Maxeiner Joachim Heinrich , Scholtes Petra , Karwot Roman , Lehr Hans Anton , Galle R. P. , Blumberg Richard Steven , Finotto Susetta 
Published: January 2023

Abstract
Epstein-Barr virus-induced gene 3 codes for a soluble type 1 receptor homologous to the p40 subunit of IL-12 that is expressed by antigen presenting cells following activation. Adoptive intravenous injection of the B16-F10 cell line resulted in a significant reduction of lung tumour metastasis in EBI-3 (−/−) recipient mice compared to wild type. Consistently, we found that EBI-3 (−/−) mice have decreased number of VCAM-1+ endothelial cells. The immunological finding accompanying this therapeutic effect was the orchestrate priming and T cell selection performed by a newly described Dendritic Cell (DC) subset called Interferon-γ producing killer Dendritic Cells (IKDC) which induced the CD8+ T cell response in the lung of EBI-3 deficient mice including Fas and TNF-α programmed tumour cell death. Finally, adoptive transfer of EBI-3 (−/−) DCs primed EBI-3 (−/−) CD8+ T cells into wild type mice decreased the number and size of lung tumour metastasis in recipient mice. Taken together, these data demonstrate that EBI-3 deficiency reduced lung tumour metastasis both because they decrease adhesion of tumour cells to lung vessels and they activate T cell mediated tumour cell apoptosis in the lung.
LAB/NTAL Regulates DAP12 Signaling and Macrophage Differentiation (B163)
Authors: Whittaker Gillian Claire , Quigley Laura , Zhang Weigou , McVicar Daniel 
Published: January 2023

Abstract
Recent studies have highlighted a significant, yet controversial role for DAP12 in the suppression of Toll receptor (TLR)-mediated inflammatory cytokine production by macrophages and plasmacytoid DC. Here we report that the Linker for Activation of T cells (LAT) and the Linker for Activation of B Cells (LAB) are critically regulated during myeloid development such that macrophages express LAB but little if any LAT. Consistent with LAB as a primary adaptor in macrophages, we readily observed its DAP12-inducible phosphorylation. Analogous to its role in Mast cells, we found that LAB also attenuates DAP12 signaling, however, the increased signaling in LAB−/− MΦ was not the result of increased utilization of LAT. Instead, LAB nucleated a DAP12-induced complex containing the E3 ligase c-Cbl and the p85 regulatory domain of PI3K. In the absence of LAB, DAP12-induced MAPK activation was ablated whereas c-Cbl was hyperphosphorylated resulting in enhanced p85/c-Cbl interactions. MΦ of DAP12 or TREM2−/− mice exhibit global increases in TLR-induced cytokine production, yet LPS stimulated LAB−/− BMM_ demonstrated increased IL-10 and decreased IL-12 p40 production. Together these data suggest that the utilization of LAB by TREM-2/DAP12 facilitates Erk1/2 activation while suppressing proximal signaling so as to yield macrophages with the appropriate balance of pro- and anti-inflammatory responses.
Hepcidin is synergistically induced in mouse macrophages by mycobacteria and IFN-γ, and is present in the mycobacterial phagosome (B166)
Authors: Sow Fatoumata Ba , Schlesinger Larry , Satoskar Abhay , Zwilling Bruce , Lafuse William 
Published: January 2023

Abstract
In mammals, infection results in the production of inflammatory cytokines and acute-phase reactants in the liver, including the synthesis of the antimicrobial peptide, hepcidin. Hepcidin controls extracellular iron by regulating its intestinal absorption and release from macrophages. It acts by binding to and mediating the degradation of the sole iron export protein ferroportin 1.
Here, we investigated the expression of hepcidin in mouse macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis H37Rv. We show that stimulation with mycobacteria and IFN-γ synergistically induce hepcidin mRNA in mouse macrophages. The induction of hepcidin mRNA by M. tuberculosis was found to be dependent on TLR2, TLR4, and STAT1. IL-6 and IL-1β, which induce hepcidin expression in liver hepatocytes, did not induce hepcidin mRNA expression in RAW264.7 cells. Iron loading, which induces hepcidin mRNA in the liver, inhibited hepcidin mRNA expression induced by IFN-γ and M. avium. These results implicate differential expression of hepcidin in macrophages and hepatocytes.
Immunofluorescence studies show that hepcidin is present in the M. avium- and M. tuberculosis-containing phagosomes. These results suggest that hepcidin production by infected macrophages is an IFN-γ induced host defense mechanism against mycobacteria.
This work was supported by grant NIH-RO1DK-57667
Innate immunity activation in mouse dendritic cells infected by Baculovirus (B188)
Authors: Hashimoto Kahoko , Suzuki Tomoyuki , Sakai Ryo , Miyazawa Yuki , Saito Ryo , Yamamoto Hiroshi , Nakayama Toshinori , Miyano-Kurosaki Naoko , Takaku Hiroshi 
Published: January 2023

Abstract
Baculovirus is an insect virus of double stranded, which has been used as a powerful tool for producing of recombinant proteins. In most cases, as mammalian cells have not been infected by the baculovirus, the infection can induce the activation in innate immunity system. For this reason, we investigated how baculovirus induce the innate immunity in the mouse bone marrow derived dendritic cells (BMDC). Among the lymphoid cells and tissues, baculovirus could activate BMDC and also macrophage cell line; RAW264.7 much more than T cells, B cells or NK cells. By the baculovirus infection, BMDC increased gene expression in many inflammatory cytokine genes, with increasing TLR genes. These results related the production of cytokines such as IL-12, IL6. IL-1 beta. These data could support our previous data, in which baculovirus infection could prevent the melanoma cells metastasis, and could recover the hepatocyte inflammation in vivo mouse models.