bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of porcine reproductive and respiratory syndrome virus neutralization from antibody production to major envelope protein peptides (49.22)
Authors: Li Juan , Murtaugh Michael 
Published: January 2023

Abstract
Porcine reproductive and respiratory syndrome (PRRS) is the most severe infectious disease facing the swine industry worldwide. The etiologic agent is PRRSV, an enveloped arterivirus. GP5 and M, the major envelope proteins, form disulfide-bonded heterodimeric complexes that are involved in PRRSV entry into porcine alveolar macrophages (PAM). Previous studies identified several neutralization epitopes in GP5 polypeptide, containing amino acid residues (AA) 29-52, and potential unknown neutralization epitopes in M protein. To test whether PRRSV-neutralizing antibodies (NA) are directed to GP5 and M ectodomain polypeptides, we constructed three recombinant single-chain proteins: the two predicted ectodomains of GP5 (GP5-5’), the two ectodomains of M (M-5’), and all four ectodomains (GP5-M). In particular, GP5-5’ contains the reported neutralization epitopes. We found that the convalescent pig sera after PRRSV infection contained various levels of antibodies to those proteins, but the Ab titers did not correlate with the NA response. Immunization of pigs with these recombinant proteins did not induce detectable NA response. Finally, protein-specific Abs that were purified from PRRSV-neutralizing serum by affinity chromatography showed no neutralizing activity, whereas the protein-specific Ab-depleted sera retained similar neutralizing activity as the original sera. The results, therefore, do not support that PRRSV-NA are directed to the ectodomain polypeptides of GP5/M.
Dendritic cells control CD4+CD25+ Treg cell function in vitro through juxtacrine delivery of IL-2. (50.3)
Authors: Field Elizabeth , Kulhankova Katarina , Rouse Todd , Nasr Mohamed 
Published: January 2023

Abstract
CD4+CD25+ regulatory T cells (Tregs) require IL-2 for their expansion and function. Unable to produce IL-2, Tregs rely on IL-2 from a neighboring cell. We explored whether DCs might serve as an important source of IL-2 for Tregs. Though a minor subset of DCs make IL-2, the IL-2 producing DCs were preferentially found in conjugate formation with Tregs. DCs continued to transcribe IL-2 in the presence of Tregs, but protein secretion was completely diverted to the Treg. Uptake of DC-derived IL-2 by Tregs involved cell:cell contact and CD25. DC IL-2 increased Tregs levels of CD25 and foxp3. Surprisingly, Treg suppressor function in vitro depended on DC IL-2. Tregs in cultures with WT DCs suppressed proliferation of CD4+ Teff more effectively than Tregs in cultures with IL-2 KO DCs. Tregs also suppressed IL-2 secretion by CD4+ Teff if cultured with WT DCs but showed no suppression if cultured with IL-2 KO DCs. In the later cultures, the transient addition of IL-2 at levels ≥ 500 U/ml restored Treg suppressor function, suggesting that DC to Treg delivery of IL-2 was spatially controlled to achieve locally high concentrations of IL-2. The findings demonstrate a clear requirement for DC-derived IL-2 for optimal Treg suppressor function in vitro and reveal a novel model of juxtacrine delivery of IL-2 from DCs to Tregs. The data lead us to speculate that IL-2 producing DCs may play a role in initiating the activation of functional Tregs in vivo through spatial delivery of signal 3.
Phenotyping human Tregs: the key to understanding autoimmunity? (50.6)
Authors: Magid-Bernstein Jessica , Rohowsky-Kochan Christine 
Published: January 2023

Abstract
T regulatory cells (Tregs) are important in the development and progression of autoimmunity. Tregs are usually identified by their expression of CD25 and Foxp3, although functionally and phenotypically diverse subsets exist. By identifying various subsets we hope to clarify their function and role in autoimmunity. We are also studying the novel cytokine IL-35, which is believed to be integral for Treg function. To identify Treg subsets we analyzed expression of CD27, CD127, and CD39 on CD4 T cells with varying CD25 levels. A CD27+CD127- phenotype correlates highly with CD25 and Foxp3 expression. CD39 expression is higher on CD4+CD25hi T cells than on CD25med/lo cells. We cultured sorted Treg subsets with T effector (Teff) cells to measure suppression. High expression of CD25 was a better marker for suppressive ability than the CD27+CD127- phenotype. CD39+ Tregs did not suppress proliferation when activated with anti-CD3 and anti-CD28, but they did inhibit IFN-γ production. Expression of the IL-35 subunits, EBI3 and p35, was observed in activated Tregs but not resting or activated induced Tregs or Teffs. Studies are ongoing to examine IL-35 in Treg subsets. Elucidating Treg mechanisms and subsets will enable us to clarify how Tregs suppress, how they are defective in autoimmunity, and ultimately how this defect can be overcome to treat autoimmunity.
Immunogenicity of a Group A Streptococcal peptide vaccine conjugated to CRM197 (53.12)
Authors: Caro-Aguilar Ivette , Ottinger Elizabeth , Hepler Robert , Nahas Deborah , Wu Chengwei , Joyce Joseph , Heinrichs Jon , Skinner Julie 
Published: January 2023

Abstract
Group A Streptococcus (GAS) causes several disease manifestations and remains a huge medical burden in developing and developed countries, therefore there is an imminent need for a prophylactic vaccine. One focal point of vaccine development for GAS has been the M protein, an alpha-helical coiled-coil surface protein. An epitope derived from the C-terminal region of the M protein, J8, has been shown to be highly immunogenic and to generate opsonophagocytic killing (OPK) activity and protection in mice. Here we evaluated the use of an alternative protein carrier, CRM197, a molecularly detoxified version of diphtheria toxoid (DT), by conjugating J8 to CRM197 and immunizing C3H and Balb/c mice with this vaccine on AAHSA (Amorphous Aluminum Hydroxyphosphate Sulfate Adjuvant). J8-specific ELISA and whole bacteria immunofluorescence (IFA) were used to evaluate immunogenicity. Functional antibody activity was evaluated by opsonophagocytosis (OPK) and protection from a GAS intranasal challenge. J8 conjugated to CRM197 induced high antibody responses to J8; these specific antibodies recognized the epitope on the surface of the bacteria by IFA and demonstrated functional activity in an OPK assay. Additionally, J8-CRM197 immunized mice demonstrated significantly greater survival than adjuvant control immunized mice. This study showed that CRM197 is a suitable carrier protein for J8 peptide conjugation in C3H and Balb/c mice.
Soluble IL-7 receptor (sCD127) in pediatric HIV infection (57.9)
Authors: Faucher Sylvie , Decker Wendy , Sherring Alice , Bogdanovic Dragica , Bergeron Michele , Mandy Francis , Lapointe Normand , Soudeyns Hugo , Sandstrom Paul 
Published: January 2023

Abstract
IL-7 is an essential cytokine in T-cell development and homeostasis. It binds to the IL-7R receptor, a complex of the IL-7Rα (CD127) and common γ (CD132) chains. There is significant interest in evaluating the expression of CD127 on human T-cells as it often decreased in medical conditions leading to lymphopenia. A soluble CD127 (sCD127) is released in plasma and may contribute to disease pathogenesis through its control on IL-7 activities. We determined the concentrations of soluble CD127 in plasma of children infected with HIV using a quantitative bead-based sCD127 immunoassay. Eleven children were followed over a period of up to two years. The sIL-7R detected in HIV infected children ranged from 66 to 1004 ng/mL. Individual sCD127 concentrations remained stable when measured serially during a period of up to two years in five children with low viral load (HIV RNA 50-500 copies/mL). In children with uncontrolled viral load (n=6) (HIV RNA 50-137 000 copies/mL), the concentrations of sCD127 varied by up to 4 fold.This is the first report on the quantification of plasma sCD127 in pediatric HIV infection. The concentrations of sCD127 in children varied by up to one log. We previously reported a similar variation among adult sCD127 concentrations. The stability of the sCD127 concentrations in children with low viral load and the variations observed in children with uncontrolled viral load warrant further studies on the sCD127 as a potential marker of T cell homeostasis.
Participation of B-1 cells in the nasal influenza vaccine-induced antibody production. (59.10)
Authors: Kouro Taku , Iida Ryuji , Hattori Yuki , Shinoda Kaori 
Published: January 2023

Abstract
Aim: Administration of vaccine via nasal route has many merits including induction of cross-protective IgA on the surface of respiratory mucosa. However there is little information about IgA producing cells in the nasal mucosa. We examined role of B-1 cells in nasal vaccination because B-1 cells are responsible for production of natural antibodies which possess wide reactivity to various pathogens. Results: B-1 cell deficient BtkKO mice and control were anesthetized and intranasally administrated with influenza HA vaccine with poly(I:C) as an adjuvant twice in 2-week interval. 2 weeks later, BtkKO mice showed significantly reduced anti-HA nasal IgA response compared to control. In contrast, when splenocytes from vaccinated mice were re-stimulated with inactivated influenza virus, cells from BtkKO mice showed same or higher response than controls in the terms of Th1 cytokine production and IFN-γ secreting cell number. Further, reconstitution of B-1 cells in the BtkKO mice resulted in partial recovery of Ig response to vaccination. Discussion: Although Btk is expressed not only in B cells but also in myeloid cells including dendritic cells, defect of B-1 cells should be responsible for the reduced nasal Ig response in the BtkKO mice because T cells in these mice were properly activated. Thus B-1 cells and their unknown regulators will be good target of potent nasal vaccine adjuvant.
Tumor-induced regulatory B cells promote cancer metastasis by inducing generation of FoxP3+ regulatory T cells (66.16)
Authors: Olkhanud Purevdorj , Bodogai Monica , Wejksza Katarzyna , Biragyn Arya 
Published: January 2023

Abstract
The involvement of regulatory and suppressive B cell has been mostly associated with control of autoimmune responses; and their role in cancer escape remains unknown. Recently we reported the existence of a unique subset of B cells that suppress T cell responses to promote lung metastasis of breast cancer. These cells, designated as tumor-evoked B cells (tBreg), were actively generated by tumor cells from normal B cells. Interestingly, number of FoxP3+ Tregs was also enhanced in tumor-bearing mice, although the mechanism of Treg expansion remains unknown. We hypothesized that tBregs induce the generation of Tregs. Utilizing in vitro and in vivo approaches, we demonstrate that tBregs indeed induce the generation of FoxP3+ Tregs from resting CD4+ T cells. The molecular mechanism of this process is that tBregs abundantly express and utilize TGFb. The generation of FoxP3+ Tregs is blocked by selective inhibition of the TGFb receptor signaling, such as by the use of TGFb-type I receptor-like kinase ALK5 inhibitor. Importantly, the tBreg-induced FoxP3+ Tregs promote lung metastasis, as proved by their adoptive transfer in NOD/SCID mice. Taken together, our data indicate that tBregs facilitate lung metastasis by inducing Tregs in a TGFb-dependent manner. Thus, the clinical implications of our findings are that, to effectively combat cancer and its metastasis, tBregs have to be controlled to interrupt the initiation of cancer-induced suppressive events.
Phenotypical and functional changes in myeloid-derived suppressor cells during the tumor progression: FKBP51 regulates the suppressive function of MDSCs (66.25)
Authors: Kim Yun-Sun , Kim Yeon-Jeong , Kim Eun-Kyung , Lee Jung-Mi , Seo Jeong-Hwan , Park Young-Jun , Kang Ho-Woong , Kang Chang-Yuil 
Published: January 2023

Abstract
Immature myeloid cells which are increased by tumor-derived factors actively suppress immune cells. Therefore, they are called as myeloid-derived suppressor cells (MDSCs). Since the effect of cancer immunotherapy would be enhanced by removing MDSCs or inhibiting their suppressive function, we tried to find a target for MDSC regulation. MDSCs were increased during the tumor progression and MDSCs of late stage tumor bearing mice had stronger suppressive activity than those of early stage tumor bearing mice, in T cell proliferation assays. To find factors that change the MDSCs during the tumor progression, we analyzed gene expression profiles in MDSCs at various tumor stages and found that expression of Fkbp5 was increased in the Mo- and PMN- MDSCs of late stage tumor bearing mice. By means of rapamycin, which inhibit the PPIase function of FKBP51 protein, we demonstrate that the FKBP51 was involved in the suppressive function of MDSCs via regulation of iNOS expression. In addition, the FKBP51 enhanced the survival of MDSCs. By targeting the FKBP51, we may regulate the suppressive function of MDSCs and enhance the effect of anti-cancer immunotherapy.
Cross-regulation of innate response in human PBMC by an enveloped RNA virus and LPS (67.11)
Authors: Dhanushkodi Nisha , Mohankumar Vidyarani , Pokkali Supriya , Raju Ramaswamy 
Published: January 2023

Abstract
The innate response to polymicrobial infections and their pathways are poorly understood. In this work, we used Sindbis virus (SIN), an enveloped RNA virus and LPS as inducers of innate response. PBMC from healthy volunteers were exposed to SIN Toto 1101, in the presence and absence of E.coli LPS. We observed absence of new virus release, SIN/GFP reporter expression and viral RNA synthesis suggesting poor replication of SIN in human PBMC. However, significant lymphocyte activation, cytokine and chemokine release were seen upon exposure of PBMC to SIN. Analysis of lymphocyte activation markers showed that, LPS was a better inducer of CD69 expression in CD4, CD8, and CD19 lymphocytes than SIN. Increased secretion of IL-12p40, IL-1β, TNF-α, IL-6, IL-18, IL-10, IL-8, RANTES, MCP-1, MIP1-α and MIP1-β was induced by LPS whereas, SIN induced IL-6, IFN-α, MCP-1, MIP1-α, MIP1-β, I-TAC and IP-10 secretion. SIN downregulated LPS induced IL-12p40 secretion, whereas LPS inhibited virus induced IFN-α and IP-10. SIN also suppressed both the spontaneous and LPS induced secretion of IFN-α, IL-17, IL-13 and SLC from PBMC. To analyze involvement of specific PBMC subsets and associated signaling events, ELISPOT and phosphoflow are used. The absence and presence of antagonism between SIN and LPS for lymphocyte activation and secretion of select cytokines and chemokines may help in understanding pathogenesis of mixed infections, and find applications in vaccine development and virotherapy.
A DV protein based in domine II and III of E protein expressed in plants induce an effective immune response (67.7)
Authors: López Moisés , Machorro Jazmin , Davila Enrique , Lim Miguel Angel , Barron Leticia 
Published: January 2023

Abstract
Dengue is the most important arboviral disease. Despite the efforts to develop an effective vaccine there is none available. In the virus the envelope protein is the most expose and it is the most immunity target. The E protein has 3 domains, the domain III (EIII) is involved in neutralizing Abs induction. Domain II (EII) contains a fusion peptide that may induce Abs with neutralizing activity. Recently Anti-DEC, has been considered as a potential adjuvant when fused with different viral proteins due to its use in targeting antigen to DCs. The goal of this work was to fuse genetically different sequences from domains II and III to heavy chain variable region of the Ab Anti-DEC-205 spaced by a flag sequence named OLLAS in order to improve the humoral response. The fusion sequences DEC-OLLAS-EII-EIII was cloned in the vector pICH31070. To express these DNA, the plants N. benthamiana were infiltrated and the protein expression was analyzed by W.B. at different days post-infiltration. The high expression was observed at day 8, then, the proteins were purify by preparative PAGE and refolded with L-arg buffer. Following groups of 8 mice were inoculated 3 times with 30μg of recombinant protein. The immunity of this protein was analyzed by ELISA, immobilizing DEN viral particles and important titer of antibodies were observed in the group of mice immunized with DEC-OLLAS-EIII-EII in contrast with the control group. Moreover neutralizing Abs was observed in the mentioned group
Dominant TNF-α Mycobacterium Tuberculosis-specific CD4 T-cell responses discriminate between latent infection and active disease (99.10)
Authors: Harari Alexandre , Rozot Virginie , Bellutti Enders Felicitas , Perreau Matthieu , Mazza Stalder Jesica , Nicod Laurent P. , Cavassini Matthias , Calandra Thierry , Lazor lanchet Catherine , Jaton Katia , Faouzi Mohamed , Day Cheryl L. , Hanekom Willem A. , Bart Pierre-Alexandre , Pantaleo Giuseppe 
Published: January 2023

Abstract
Background: Diagnosis of Mtb infection requires several parameters. IFNg-release assays do not discriminate between active TB disease and latent Mtb infection. Methods: Mtb-specific T-cell responses were investigated in a test cohort of 283 subjects with known diagnosis of latent Mtb infection or active TB disease and subsequently in a validation cohort of 114 subjects with blinded clinical status. Mtb-specific T-cell responses were analyzed by polychromatic flow cytometry using ESAT-6 and CFP-10 peptide pools. Results: Mtb-specific IFNg ELISpot responses were not different between patients with active TB disease or latent Mtb infection. In contrast, the functional profile of Mtb-specific CD4 T-cell responses was significantly different between active TB disease and latent Mtb infection (ESAT-6 or CFP-10, all P&lt;0.0001) in the test cohort. Overall, Mtb-specific CD4 T-cell responses from patients with latent Mtb infection were TNFa+IFNg+IL-2+, while single TNFa-producing Mtb-specific CD4 T-cell responses were dominant in patients with active TB disease. Using this parameter (i.e. % of single TNFa-producing cells) as a diagnostic tool in an independent cohort of 101 patients with blinded TB diagnosis, we obtained &gt;90% concordance between the clinical and the cytokines profile in predicting active TB disease and latent Mtb infection Conclusions: Polychromatic flow cytometry is a novel and reliable laboratory tool for the timely diagnosis of acute TB disease.
Presence of long lived bone marrow effector cells mediate protection against a virulent bacterial pathogen (99.30)
Authors: Anderson Rebecca , Crane Deborah , Bosio Catharine 
Published: January 2023

Abstract
Francisella tularensis is a virulent bacterium that causes lethal disease in humans. The cellular response that protects against a virulent Francisella infection (SchuS4) is not clearly understood. Live vaccine strain (LVS) vaccination in animal models confers nearly 100% protection against SchuS4 challenge; unfortunately, the mechanism of protection is not well defined. Therefore, the goal of this project is to determine the population and location of anti-Francisella effector cells that develop 3 months after LVS vaccination. The ability of cells from the spleen, bone marrow, liver, draining lymph node and blood of LVS vaccinated mice were assessed for limiting in vitro replication of SchuS4 in macrophages. Surprisingly, bone marrow cells from LVS vaccinated mice significantly reduced SchuS4 replication; however, cells from blood, spleen, liver, and lymph nodes did not control infection. The bone marrow is a unique environment that maintains memory B and T cells, as well as facilitates NK cell development. Therefore, CD90.2+ cells were purified, which represent B, T and NK cells. CD90.2+ cells reduced the total number of SchuS4 infected macrophages by nearly 50%, compared to CD90.2- cells. Upon further purification, CD49b cells elicited control of SchuS4 infected macrophages. These results suggest the effector population may be an NK, NKT, killer DC or T cell that mediates in vitro control of SchuS4 infection of macrophages.
Pseudomonas aeruginosa reduces the immune response to respiratory viruses (99.33)
Authors: Bomberger Jennifer , Ely Kenneth , Bangia Naveen , Berwin Brent , Green William , Enelow Richard , Stanton Bruce 
Published: January 2023

Abstract
P. aeruginosa chronically colonizes the respiratory tract of patients with chronic obstructive pulmonary disease, bronchiectasis and Cystic Fibrosis. These patients experience debilitating and life-threatening viral exacerbations of unknown etiology. Cif, a bacterial toxin secreted by P. aeruginosa, promotes the degradation of several ABC transporters involved in innate immunity, including CFTR and Pgp. The current study tests the hypothesis that Cif enhances the degradation of the transporter associated with antigen processing (TAP), resulting in reduced adaptive T-cell responses to viral pathogens. Cif inhibited the deubiquitinating enzyme, ubiquitin specific protease 10 (USP10), resulting in a time-dependent increase in the polyubiquitination and proteasomal degradation of TAP1. Cif inhibited USP10 activity by stabilizing an inhibitory protein-protein interaction between USP10 and G3BP1. The Cif-mediated decrease in TAP1 expression resulted in decreased MHC class I viral antigen presentation, CD8+ cytotoxic T lymphocyte (CTL) recognition of influenza virus-infected cells and dramatically reduced MHC class I cell surface levels on CD11c+ cells in the BAL of mice treated with P. aeruginosa. We propose that P. aeruginosa, by secreting the Cif toxin, inhibits the ability of CTL to recognize and eliminate viral infections, severely compromising the immune defenses of the lung. This is the first identified bacterial toxin that inhibits the viral immune response of the host.
Interleukin-10 limits RSV-induced disease severity by modulating the virus-specific T cell response (105.4)
Authors: Weiss Kayla , Christiaansen Allison , Fulton Ross , Meyerholz David , Varga Steven 
Published: January 2023

Abstract
The host immune response contributes to the severity of pulmonary disease following acute respiratory syncytial virus (RSV) infection. IL-10 is a potent immunomodulatory cytokine produced by multiple CD4 T cell subsets following RSV infection. We hypothesized that IL-10 negatively regulates the RSV-specific immune response thereby limiting disease severity. We observed that peak viral replication and clearance is not altered by the absence of IL-10 or following IL-10R blockade. However, disease severity as measured by weight loss and airway resistance is significantly increased in the absence of IL-10 or following IL-10R blockade following acute RSV infection. Histological analysis indicates that following IL-10R blockade there is an increase in mucus production and inflammation in the lung airways. We also observed a significant increase in pro-inflammatory cytokines and chemokines in the absence of IL-10 following RSV infection. Moreover, the total number of the IFN-γ-producing CD8 and CD4 T cells responding to the infection are significantly increased following IL-10R blockade. Interestingly, IL-10R blockade during RSV infection also altered CD4 T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4 T cells and a concomitant decrease in Foxp3+ regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury.