bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokines production by PBMC from pregnant and non pregnant women after addition lives tachyzoites of Toxoplasma gondii (67.9)
Authors: de Oliveira Karine , Alves Silva Jéssica , Peghini Bethânea , Silva Marcos Vinicius , Gómez-Hernández César , Silva Neide , Mineo José Roberto , Rodrigues Junior Virmondes 
Published: January 2023

Abstract
Introduction: During pregnancy, mother’s immune system modulates immune response in order to allow the maintenance of fetal tolerance. Besides, this tolerogenic environment the adaptative immune response exist and are effective against microbes such as T. gondii, causative agent of toxoplasmosis. Objective: Evaluate the production of cytokines by PBMC from parturient and non-pregnant women exposed to live tachyzoites ME49 strain of T. gondii. Methods: PBMC from 31 parturient, which 21 were T. gondii IgG+ and 22 non-pregnant women, where 8 were T. gondii IgG+ were cultivated (105cells/well) in presence of anti CD3 or live tachyzoites (2 parasites/cell) of T. gondii ME49 strain. The cells were incubated for 72h and cytokine titration by CBA in supernatants. Results: The cytokine’s levels produced by parturient’s cells and non pregnant women showed existence of correlation between the production of Th2 and Th1 cytokines on live tachyzoites culture, independent of group or serology: IL4/TNF-α (r=0.51, p&lt;0.05), IL5/TNF-α (r=0.68, p&lt;0.05), IL5/IFN-γ (r=0.28, p&lt;0.05), IL10/TNF-α (r=0.89, p&lt;0.05) and IL10/IFN-γ (r=0.50, p&lt;0.05). The group with previous exposure to parasite (IgG+) presented correlation between the cytokines: IL4/TNF-α (r=0.70, p&lt;0.05), IL5/TNF-α (r = 0.81, p&lt;0.05) and IL10/TNF-α (r=0.90, p&lt;0.05). Conclusion: T. gondii induces pro or anti-inflammatory cytokines production independent of patient’s pregnancy condition or previous exposition to parasite.
Loss of the ITAM receptor CD200R1 attenuates HSV-1 infection and encephalitis. (68.15)
Authors: Kurt-Jones Evelyn , Soberman Roy , Vaine Christine , Mackay Christopher , Ryan Glennice , Knipe David 
Published: January 2023

Abstract
We have discovered a novel role for the Immunoreceptor tyrosine-based activation motif (ITAM) containing receptor CD200R1 in virus infection. The host response to viral pathogens is driven by the activation of innate immune receptors that are triggered by pathogen-associated molecular pattern (PAMPs). These receptors include the transmembrane Toll-like receptors as well as the intracellular nucleic acid sensors RIG-I, Mda5, AIM2 and IFI16. ITAM receptors are known to both attenuate and activate signaling by innate receptors like TLRs but little is known about the potential impact of ITAMs on the outcome of viral infection. We generated CD200R1 knockout (KO) mice and infected with herpes simplex virus (HSV)-1. CD200R1 KO mice were protected from lethal HSV-1 encephalitis with &gt;75% of the CD200R1 KOs surviving compared to 25% of the wild type (WT) mice, i.e., loss of CD200R1 conferred a survival advantage. This was not due to any obvious effects on the inflammatory response to infection. CD200R1 KO and WT mice had equivalent cytokine responses and leukocyte infiltration during the initial infection. Remarkably, HSV-1 virus replication was attenuated in CD200R1 KOs. Thus 50% of the CD200R1 KOs had cleared the virus from their brain by day 3-4 post-infection. In contrast, HSV-1 continued to replicate in the brains of 100% of the WT mice. Infection of cultured cells confirmed that CD200R1 expressing WT cells were more permissive for HSV-1 infection than CD200R1 KO cells.
Role of granulysin in MDP-induced PGE2 production in human monocytes (68.2)
Authors: Endo Yukinori , Zaitseva Marina , Romantseva Tatiana , Golding Hana 
Published: January 2023

Abstract
Muramyl dipeptide (MDP) is a NOD2 agonist known to induce pyrogenic response in vivo in humans and in animal models. The mechanism of MDP-induced fever was studied in vitro in human primary cells by measuring PGE2, a final mediator of febrile response. Elutriated monocytes produced significant levels of PGE2 following stimulation with LPS but not MDP. However, addition of human CD3 bead-purified T cells significantly augmented COX2 mRNA expression and PGE2 protein production in MDP-activated monocytes. PI3 kinase inhibitor LY294002 and ROS inhibitor DPI all inhibited PGE2 production and COX2 mRNA up-regulation. Studies using trans-well system confirmed that PGE2 production in MDP-activated monocytes did not require direct cell to cell contact between monocytes and T cells. Anti-IFN gamma antibodies did not inhibit the effect of T cells suggesting that factor(s) other than IFN gamma play a role in MDP-induced PGE2 production in monocytes. Jurkat cells did not deliver the missing factor required for PGE2 production in MDP-activated monocytes. cDNA microarray analysis revealed high levels of Granulysin (GNLY) mRNA expression in bead-purified T cells but not in Jurkat cells. Recombinant GNLY induced high levels of PGE2 in monocytes activated with MDP and the effect of GNLY was sensitive to ROS and PI3K inhibitors. In conclusion, our data suggest that GNLY might be one of the molecules that are produced by T cells and contribute to PGE2 production by MDP-activated monocytes.
Molecular mechanisms of Innate DNA recognition by the AIM2 and IFI16 inflammasomes (68.4)
Authors: Jin Tengchuan , Perry Andrew , Jiang Jiansheng , Smith Patrick , Curry James , Unterholzner Leonie , Jiang Zhaozhao , Horvath Gabor , Rathinam Vijay , Hornung Veit , Johnstone Ricky , Latz Eicke , Bowie Andrew , Fitzgerald Katherine , Xiao T. 
Published: January 2023

Abstract
Structures of The HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of The AIM2 Inflammasome and IFI16
FLAGELLIN-DEPENDENT AND INDEPENDENT INNATE IMMUNE RESTRICTION OF LEGIONELLA PNEUMOPHILA INFECTION IN VITRO AND IN VIVO (68.5)
Authors: Lima Jonilson , Pereira Marcelo , Zamboni Dario 
Published: January 2023

Abstract
Recognition of L. pneumophila flagellin by Naip5-Nlrc4 inflammasome is required for innate immune restriction of the infection in restrictive mice background. Therefore, regardless to the mice background, flaA- mutant bacteria can be used to screen for important components of the immune system that account for growth restriction. flaA- bacteria were used to systematically infect mice and macrophages deficient for: 1) molecules important for effectors mechanisms of immune response (IFNγ, IL-6, 10, 12, 17, 18, 23, MIP-1α and TNFRp55); 2) cells of immune response (CD4KO-MHCII-/-, CD8KO-β2m-/-, BKO and neutrophils-anti-LY6G); 3) transmembrane innate immune receptors (CCR2, CCR4, Fas/Fas-L, ST2-, TLRs-); and 4) intracellular signaling molecules (PI3k, MyD88, Nod1, Nod2 and Rip2). Our data shows that mechanisms related with innate immune response, but not adaptive response are important for bacterial growth restriction in vivo and in vitro. Activation of these responses are critical for bacterial growth restriction and resolution of pulmonary infection in a murine model of Legionnaires’ disease.
The role of SIRT1 in the activation of innate immune responses during RSV infection (68.6)
Authors: Owczarczyk Anna , Petersen Bryan , Schaller Matthew , Reed Michelle , Demoor Tine , Mukherjee Sumanta , Ptaschinski Catherine , Morris Susan , Lombard David , Lukacs Nicholas 
Published: January 2023

Abstract
Respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infection in infants and children worldwide. Dendritic cells (DC) prime the adaptive immune response by recognizing and delivering viral antigens to local lymph nodes, presenting antigen to T cells, displaying co-stimulatory markers, and releasing cytokines. Recent studies have linked macroautophagy to intracellular pathogen recognition and the activation of DCs leading to enhanced antigen-presenting cell (APC) function. SIRT1, a NAD+ dependent deacetylase, acts on many cellular substrates, including autophagy proteins (Atg), as shown with Sirt1-/- mice that accumulate damaged organelles similar to Atg5-/- mice. Our study investigates the role of SIRT1 in DC maturation, subsequent T cell activation, and RSV-induced pulmonary pathology. RSV infected bone marrow-derived DCs (BMDC) pre-treated with EX-527, a SIRT1 inhibitor, downregulate expression of key cytokines, MHCII, and CD86. EX527 treatment of RSV- infected wild-type mice resulted in increases in lung mucus production, viral load, and TH2 cytokine production. Likewise, EX527 significantly antagonizes TLR7-induced cytokine release in RSV-infected BMDCs, suggesting a link with the TLR/PAMP recognition response. These results suggest that SIRT1 may be a critical determinant in the innate immune response and resultant pulmonary pathology during RSV infection.
The role of nucleotide-binding oligomerization domain 2 (Nod2) in initiation of rheumatoid arthritis. (68.7)
Authors: Franca Rafael , Peres Raphael , Talbot Jhimmy , Cunha Thiago , Cunha Fernando 
Published: January 2023

Abstract
The etiology of several inflammatory diseases such as rheumatoid arthritis (RA) remains unknown. Some studies including data from our group, report that the receptor NOD2, a member of NLR family, is overexpressed in synovial fibroblasts of patients with RA. Since NOD2 activation might contribute to the initiation and perpetuation of chronic destructive inflammation in RA, we decided to investigate the role of this receptor in arthritis. Initially, WT and NOD2-/- mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA. Our data shows that knockout NOD2 mice did not develop arthritis, as evidenced by the low number of infiltrating cells into the articular cavity, and that transfer of wild type neutrophils into NOD2-/- mice did not restored the inflammatory status. Additionally, to assess if synovial fluid of RA patients could activate NOD2 in vitro, HEK293-Luciferase-NF-κB cells were transfected with a plasmid encoding the NOD2 receptor, 24 hours later these cells were stimulated with MDP or synovial fluid in different concentrations, osteoarthritis synovial fluid were used as control. Luciferase activity was measured 8 hours after stimulation. We observed that stimulation of NOD2 transfected cells with synovial fluid from RA patients leads to increased luciferase activity, suggesting the NF-κB activation dependent of NOD2 signaling in HEK293 cells. Together, these results suggest that NOD2 receptor has an important role in the pathogenesis of RA.
Characterization of the functional role of VAMP8 in granule exocytosis of T lymphocytes (69.12)
Authors: Marshall Misty , Pattu Varsha , Halimani Mahantappa , Maier-Peuschel Monika , Hoth Markus , Rettig Jens 
Published: January 2023

Abstract
One salient event in the adaptive immune response is the activation of T lymphocytes by foreign antigens. They patrol our body for providing a defense against intracellular pathogens, viruses and malignant cells. Upon recognition, T lymphocytes exert their cytotoxic activity through secretion of cytotoxic granules at a specialized cell interface, the immune synapse (IS), or engage in stimulus-coupled release of immune mediators in pre-formed granules. To induce target cell death, T lymphocytes rely on exocytosis of granules, which is the result of a cascade of events consisting of docking, priming, and finally Ca2+-dependent fusion involving soluble NSF attachment receptor (SNARE) proteins. VAMP8 is a SNARE protein that is a key component of a variety of secretion in other immune cell types and whose function in T cell killing is unknown. VAMP8 re-localizes to the immunological synapse following CTL activation suggesting it plays an important role in granule fusion. VAMP8 has also been shown to localize abundantly at the membranes of early and late endosomes. Additionally, VAMP8 plays a role in the exocytosis of organelles formed in the secretory pathway, such as exocrine granules and secretory lysosomes. Hence, this research is aimed at elucidating the involvement of VAMP8 in T lymphocytes of secretory granule release allowing us to better understand the contribution of VAMP8 to the killing process of T lymphocytes.
CD47low status on CD4 effectors is necessary for the contraction of the immune response in humans and mice (69.13)
Authors: Van Vu Quang , Baba Nobuyasu , Rubio Manuel , Wakahara Keiko , Panzini Benoit , Richard Carole , Susin Genevieve , Franchimont Denis , Fortin Genevieve , Martinez Torres Ana Carolina , Cabon Lauriane , Susin Santos , Sarfati Marika 
Published: January 2023

Abstract
To execute a memory program, CD4 effector T cells must escape cell death and elimination and survive beyond the contraction of the immune response (IR). The involvement of Fas/FasL in the crash of IR has been challenged and the elimination of CD4 effector T cells appeared to occur independently of caspase activation. We report here that in vitro TCR-activated human CD4 T and ex vivo isolated effector memory T cells displayed a CD47low status that was linked to thrombospondin-1/CD47-induced caspase-independent cell death. By contrast, a CD47highstatus that was observed on central memory T cells and on activated CD4 T cells cultured in the presence of IL-2 correlated with resistance to CD47-mediated killing. A CD47low status was required on murine antigen (Ag)-specific CD4 effectors T cells for the contraction of the IR in vivo, as lower numbers of Ag-specific CD47low CD4 T cells were recovered when compared to Ag-specific CD47-/- CD4 T cells. Finally, the maintenance of a CD47high status on CD4 effectors despite high level of TSP-1 production was observed in inflamed tissues of patients with Crohn’s disease when compared to non-IBD donors, suggesting that a CD47high status on tissue-destructive CD4 effectors prevents the resolution of inflammatory response. In conclusion, a transient change in the status of the self-marker CD47, i.e. from CD47high to CD47low, regulates the decision-making process that leads to cell death during the IR.
The antigen dose regulates T-cell fate by controlling the B-cell response (69.2)
Authors: Kalies Kathrin , Stamm Claudia , Westermann Juergen 
Published: January 2023

Abstract
The nature of the antigen determines the type of T-cell response and thereby the course of the resulting immune reaction. Especially, the binding affinity of the peptide-MHCII complex to the T-cell receptor and the presence of cytokines are crucial. In addition, it has been reported that the antigen dose used for immunization regulates T-cell fate. For example, intravenous priming with sheep red blood cells (SRBC) induces two functionally distinct T-cell populations. A high dose (10e9 SRBC) induces T cells that provide B cell help (Th2 cells) whereas a low dose (10e5) induces T helper cells that mediate delayed type hypersensitivity reaction in the skin (Th1 cells). The mechanism behind the induction of Th1 or Th2 cells is not well understood. In this study, we investigated the expression of Th1 and Th2 cytokines in the compartments of the spleen in vivo using laser microdissection and real-time RT-PCR to understand how these distinct T-cell populations are formed. Our results show that cytokine producing effector T cells appear in the spleen only after high dose priming and only in the presence of activated B cells. In contrast, T cells induced by a low dose do not start to produce cytokines in the spleen but after encounter SRBC in the skin. We conclude that the induction of cytokine producing effector T cells requires a second contact between T cells and SRBC, which is given by B cells in the spleen after high dose priming and in the skin after low dose priming.
POU2AF1(+) follicular helper T (Tfh) cells in obstructive sleep apnea syndrome (OSAS) (69.3)
Authors: Ichimiya Shingo , Matsumiya Hiroshi , Kubo Terufumi , Ara Shihoko , Ye Rui , Sato Akinori , Kikuchi Tomoki , Yamashita Keiji , Mitsuhashi Yukari , Seki Nobuhiko , Shirasaki Hideaki , Kimura Sachiko , Yokoyama Shigeaki , Sato Noriyuki , Himi Tetsuo 
Published: January 2023

Abstract
OSAS is attributable to periodic collapse of the upper airway due to adenotonsillar hypertrophy, featuring prominent germinal centers and wide interfollicular zones. However, the mechanism is still unclear. Here we present the possible involvement of Tfh cells in the pathogenesis of OSAS as indicated by comprehensive analysis of tonsillar lymphocytes of OSAS patients. The results revealed that tonsillar Tfh cells were plentiful in OSAS compared to recurrent tonsillitis (RT) without any discrepancy of T-cell components between the tonsils of OSAS and RT patients, indicating a ‘Tfh shift’ in OSAS tonsils. In addition, in vitro experiments delineated a unique function of the Tfh cells of OSAS, which could help expand the number of naive B cells and, more extensively, memory B cells, which allowed the Tfh cells to produce larger amounts of IL-4 and IFN-γ. Microarray studies newly identified transcripts characterizing the Tfh cells, including TIGIT and POU2AF1 regulating CXCR5 of B cells. Indeed, B-cell expansion was under the control of TIGIT, and large numbers of POU2AF1(+) Tfh cells were observed in and outside of germinal centers of OSAS tonsils. Overall these findings indicate that POU2AF1(+) Tfh cells cooperate with regional B-cell subsets to induce lymphoid hyperplasia.Focusing on the TIGIT-selective regulation of POU2AF1(+) Tfh cells, further investigations may provide a new modality for a noninvasive approach to treatment of this condition.
RANK-ligand activates stroma in postnatal lymph node growth (69.4)
Authors: Mueller Christopher , Hess Estelle , Golub Rachel , Choi Yongwon , Hideo Yagita 
Published: January 2023

Abstract
The lymph node (LN) is a well-organized immune organ, favoring immune cell interactions in a spacio-temporally-controlled manner. Studies of embryonic LN formation have identified TNFSF11 (RANKL), the lymphoid tissue inducer cells and the fibroblastic stromal cells as key players in this process. Yet the cellular and molecular mechanisms that underlie postnatal LN growth remain unclear. We have studied a mouse mutant overexpressing RANKL in the skin and found massive postnatal growth of skin-draining LNs. T cells and dendritic cells are not activated and respond well to immunization by foreign antigen and adjuvant. The overall organ architecture is preserved with the exception of an increase in the numbers of small B cell follicles. Reticular fibroblastic and vascular stromal cells, important for secondary lymphoid organ formation and organization, express RANK and undergo hyperproliferation, which is abrogated by RANKL neutralization. In addition, they express higher levels of CXCL13 and CCL19 chemokines as well as MAdCAM-1 and VCAM-1 cell adhesion molecules. As for hematopoietic cells, they appear to receive anti-apoptotic signals as T cells from hyperplasic LNs survive better in lymphopenic hosts than T cells from control mice. These findings identify RANKL as a key molecule for controlling homeostasis of the immune system through stroma.
The role of CD11c in IL-17A and IL-22 production in innate A. fumigatus infection (70.10)
Authors: Gessner Melissa , Lilly Lauren , Dunaway Chad , Bullard Daniel , Steele Chad 
Published: January 2023

Abstract
We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to A. fumigatus lung infection in the presence of lower IL-17A and IL-22 production in the lungs. Our data suggests that IL-23 contributes to most, but not all, Il-17A and IL-22. As the presence of CD11b+ and CD11c+ cells are required for optimal IL-17A production by neutrophils (Werner, et al.), we examined the role of the CD11b and CD11c receptors in lung cell production of IL-17A and IL-22 during A. fumigatus infection. Here, we show that CD11c deficiency, and CD11b deficiency to a lesser extent, results in compromised IL-17A and IL-22 production by lung cells from A. fumigatus challenge mice. We further observed a contribution for CD11c in the production of IL-1a, IL-1b and TNF-a as well as neutrophil recruitment during A. fumigatus infection. Despite impaired levels of IL-17A and IL-22, CD11c deficiency did not result in impaired Il23 mRNA levels. Collectively, our results indicate that CD11c is required for optimal IL-17A and IL-22 production in early innate lung defense against A. fumigatus, although this defect is not a result of impaired IL-23 induction.
BAFF neutralization blocks T cell-independent IgM production (70.3)
Authors: Jones Derek , Jones Maura , DeIulio Greg , Racine Rachael , Winslow Gary 
Published: January 2023

Abstract
Infection of mice with the intracellular bacterium Ehrlichia muris induces a protective T cell-independent (TI) IgM response. The TI IgM produced during acute infection is secreted almost exclusively by a population of CD11c-expressing B cell plasmablasts in the spleen. We investigated the role of B cell activating factor of the TNF family (BAFF) on the generation of the IgM-secreting plasmablasts. To this end, we neutralized BAFF in vivo using a monoclonal antibody directed against murine BAFF. Blockade of BAFF in infected mice did not affect the generation of splenic plasmablasts; however, treatment nearly eliminated the number of antigen-specific IgM-secreting cells, serum IgM titers were reduced, and the plasmablasts failed to express cell-surface CD138. Analysis of mRNA expression in FACS-sorted plasmablasts from anti-BAFF and isotype control-treated mice revealed no differences in transcript levels of prdm1 and xbp1, genes encoding the transcription factors Blimp-1 and XBP-1, which are essential for plasma cell differentiation. Thus, our data indicate that BAFF signaling regulates a checkpoint in plasmablast differentiation, downstream of Blimp-1 and XBP-1 transcription, but prior to CD138 expression.
Intestinal mast cell progenitors function as innate lymphoid cells (P497) (71.3)
Authors: Lee Youngae , Kumagai Yutaro , Akira Shizuo , Jang Myoung Ho 
Published: January 2023

Abstract
Small intestinal innate lymphoid cells (mainly NKp46+ILCs) are known to have a protective role from infection of pathogenic bacteria through the production of IL-22. The proportions of ILCs localized intestinal lamina propria are higher than those in the others lymphoid tissues, such as mesenteric lymph node, spleen, liver, and bone marrow. In this study, we did a microarray experiment to study whether small intestinal ILCs (Lin-c-Kit+Sca-1- cells) highly express which genes as compared with non-ILCs (Lin-c-Kit-Sca-1- cells). We selected 251 up-regulated genes and 219 down-regulated genes in Lin-c-Kit+Sca-1- cells. Especially, Lin-c-Kit+Sca-1- cells highly expressed genes coding to Il22, Csf2rb2, mast cell proteases (Mcpts), and Rorc. To address whether which ILC populations are main source of IL-22, we more detailed divided Lin-c-Kit+Sca-1- cells into the two groups [Lin-c-Kit+NKp46+ (NKp46+ILCs) and Lin-c-Kit+NKp46-CD4-]. Only Lin-c-Kit+NKp46-CD4- cells expressed Csf2rb2 and Mcpts transcripts. These cells expressed higher level of Il22 mRNA, IL-22 protein, and IL-17F protein in physiological condition and in IL-23 stimulated condition compared with NKp46+ILCs. Moreover, these cells could differentiate into mast cells in the presence of mIL-3 and mSCF. Taken together, Lin-c-Kit+NKp46-CD4- cells as mast cell progenitors may regulate small intestinal homeostasis through the production of Mcpts, IL-17F, and IL-22 in physiological condition and in pathophysiological condition.