bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Efficacy of miniKexin DNA versus protein vaccination against Pneumocystis infection. (166.13)
Authors: Elsegeiny Waleed , Zheng Mingquang , Yu Amy , Kolls Jay 
Published: January 2023

Abstract
Pneumocystis Pneumonia (PCP) is a leading cause of death in individuals with AIDS or other immunocompromised conditions. We have previously shown that mice vaccinated with DNA encoding full-length PC antigen Kex1 have approximately a three-log reduction in PC organism burden after challenge. Full length Kex1 is poorly expressed so to improve on this we developed codon optimized vectors expressing a truncated conserved form of Kex1, mini-kexin. This also allowed investigation of a prime boost strategy since mini-kexin could be efficiently packaged into recombinant adenovirus. Mice were vaccinated with DNA encoding mini-kexin followed by boosting with adenovirus, CD4+ T cells were then depleted by GK1.5, and finally the mice were challenged with live Pneumocystis. The results showed significantly reduced PC burden in vaccinated mice. We then proceeded to generate a protein-based, E coli produced vaccine, however, this time vaccine elicited similar anti-Kex1 titers but lacked protection. We hypothesize that post-translational modification such as glycosylation could play a role in the efficacy of mini-kexin vaccination.
Memory T cells convert tissue resident myeloid cells into APCs during clearance of a persistent viral infection (166.28)
Authors: Herz Jasmin , McGavern Dorian 
Published: January 2023

Abstract
Persistent viral infections are often very difficult to treat in humans. Adoptive immunotherapy is an approach that involves administration of anti-viral T cells and has shown some promise in the clinic. Our laboratory models adoptive immunotherapy by transferring anti-viral memory T cells into mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV). Here, we demonstrate that memory T cells can completely purge the brain of persistently infected mice without causing immunopathology or blood brain barrier breakdown. Memory T cells accomplish this by inducing a tailored release of chemoattractants that recruit adaptive immune cells, but few pathogenic innate immune cells (e.g. neutrophils and inflammatory monocytes) into the nervous system. Memory T cells also enlist the support of nearly all brain resident myeloid cells (referred to as microglia) by converting them into CD11c-expressing antigen-presenting cells (APCs). Following conversion, CD11c+ microglia release CCL5 and promote interactions with therapeutic memory T cells in the brain parenchyma. Our two photon imaging studies revealed that anti-viral CD8 T cells are more likely than CD4 T cells to decelerate and form stable interactions with brain-resident APCs. We propose that non-cytopathic viral clearance from the brain by therapeutic memory T cells results from tailored chemoattractant production and conversion of resident myeloid cells into CD11c+ APCs.
Adjuvant-free nanogel-based PspA nasal vaccine for the induction of protective immunity against Pneumococcus (166.7)
Authors: Yuki Yoshikazu , Kong Il , Sato Ayuko , Nochi Tomonori , Mejima Mio , Kurokawa Shiho , Hiroiwa Tomoko , Fukuyama Yoshiko , Sawada Shinichi , Takahashi Haruko , Akiyoshi Kazunari , Kiyono Hiroshi 
Published: January 2023

Abstract
To establish strategically effective and attractive vaccine against pneumococcal respiratory infections, combining the current knowledge and technology for common antigen throughout pneumococcal strains and the new delivery system is essential. Here, we introduce a new pneumococcal nasal vaccine using the advantages of Pneumococcal surface protein A (PspA) antigen and a new adjuvant-free intranasal vaccine-delivery system with a nanometer-sized hydrogel (nanogel) consisting of a cationic type of cholesteryl group-bearing pullulan (cCHP). Nanogel-based PspA nasal vaccination induced high levels of antigen-specific serum IgG, and nasal and bronchial secretory IgA (SIgA) antibodies. The levels of PspA-specific antibodies were as high as those in mice nasally immunized with PspA and mucosal adjuvant, cholera toxin. The nanogel induced PspA-specific immune responses provided protective immunity against the lethal challenge with Streptococcus pneumoniae Xen10. Nanogel-PspA vaccinated group thus had less numbers of pneumococcus on the surface of the bronchial mucosa, and perfectly protected from the pneumococcal invasion of the lung parenchyma. These results demonstrate the effectiveness of the nanogel-based PspA nasal vaccine system as an adjuvant free mucosal vaccine against the respiratory infection of pneumococcus.
Anti-Group B streptococci Ib antibodies protect against invasive aspergillosis. (166.9)
Authors: Wharton Rebekah , Dizon Brian , Kearney John 
Published: January 2023

Abstract
Aspergillus fumigatus (A.f.) the cause of invasive Aspergillosis (IA) has become a leading cause of death in immunosuppressed populations, due to the lack of effective therapies or vaccines. Studies using anti-A.f. monoclonal antibodies indicate that they can protect against IA. However, the lack of detailed information on the antigenic targets of protective anti-A.f. antibodies has hampered the development of an effective anti-A.f. vaccine. Sialylated epitopes found on a variety of pathogens including fungi and Group B Streptococci (GBS) are thought to be major virulence factors and are involved in attachment to host cells, uptake by phagocytes, and complement activation. Sialylated epitopes on A.f. may therefore provide a potential target for new therapies. Our preliminary data show that a purified, calcium-dependent GBSIb type-specific antibody, SMB19 (IgM,κ) also binds to A.f. and prolongs survival in a murine model of IA. Similarly, immunization of wild type and SMB19 VH bearing immunoglobulin transgenic mice with a GBSIb vaccine also provides protection. These results support our hypothesis that induction of GBSIb specific antibodies, perhaps supplemented with antifungal drugs, will lead to new vaccines or passive antibody prophylaxis to prevent and treat IA.
Insights into MHC evolution provided by interesting genes on Gallus gallus chromosome 16 (167.10)
Authors: Miller Marcia , Zhang Lei , Goto Ronald , Abernathy Jason , Zhou Huaijun , Delany Mary 
Published: January 2023

Abstract
The MHC is viewed as ancient and polymorphic as result of enduring selection by diverse pathogens. But even now little is known about MHC polymorphism outside of a few mammalian species. There is little evidence as to how this region contributions in resistance to infectious disease. The MHC of the domesticated chicken (Gallus gallus) has long been observed to influence disease resistance. With a significant portion of the G. gallus MHC sequenced it is now possible to begin to examine individual loci in detail. Our studies have provided evidence for three diverse features contributing to G. gallus MHC diversity and polymorphism: 1) It has become clear that chicken natural killer cells distinguish among different MHC class I isoforms. Natural killing of target cells can be stimulated or inhibited by the expression of different MHC class I alleles. So it seems that innate immunity likely contributes to the long-observed association between chicken MHC haplotype and disease. 2) Expression of BG1, a polymorphic MHC inhibitory receptor contributing in MHC-linked resistance to a herpesvirus-induced lymphoma, is modulated in at least one allele by a retroviral insert targeted by endogenous miRNA. 3) By combining trisomy mapping with array Comparative Genomic Hybridization (aCGH) we have been able to assign to chicken chromosome 16 unmapped genomic sequence contigs containing additional genes long posited to be critical in maintaining pathogen selected MHC diversity.
Transcription factor E2F1 suppresses dendritic cell maturation. (167.3)
Authors: Fang Fang , Wang Yan , Li Rui , Zhao Ying , Guo Yang , Jiang Ming , Sun Jie , Ma Yang , Ren Zijia , Tian Zhigang , Yang De , Xiao Weihua 
Published: January 2023

Abstract
Recent studies report that transcription factor E2F1 regulates a number of genes in macrophage in response to immune stimulus, and involves in regulating T cell proliferation and differentiation. These studies indicate that E2F1 has impacts on the immune regulation additionally to its roles of regulating cell cycle and apoptosis. Our work shows that during the lipopolysaccharides (LPS) induced dendritic cell (DC) maturation, the level of E2F1 expression was transiently down regulated. The further study showed that knockdown of E2F1 induced both phenotypic and functional maturation in DCs. Conversely, DCs maintained in immature state when E2F1 was ectopically overexpressed. Moreover, E2F1 induced activation of multiple signaling pathways including PI3K, Erk1/2, NF-kappaB, which are generally thought to be involved in DC maturation. Overall, our study demonstrated that E2F1 served as a negative feedback factor to prevent overreaction in DC maturation.
DUSP11 is required for innate immunity (167.4)
Authors: Nallaparaju Kalyan , Zhang Yongliang , Liu Xikui , Reynolds Joseph , Nurieva Roza , Dong Chen 
Published: January 2023

Abstract
Dual specificity phosphatases (DUSPs) have been shown to play a critical role in regulation of various cellular processes. DUSP11 was previously demonstrated to bind to RNA-RNP complexes and RNA splicing factors and is a p53 target gene. Our in vitro studies showed that DUSP11 expression is induced in dendritic cells (DCs) upon stimulation by TLR ligands and in T cells upon CD3/CD28 activation suggesting the prominence of DUSP11 in immune responses. To examine the function of DUSP11 in regulating immune responses, we generated and analyzed DUSP11 deficient mice. We found that DUSP11 deficient antigen presenting cells produce decreased levels of proinflammatory cytokines during innate immune responses and CD4 T cells showed increased proliferation after activation but no apparent defect in in vitro T cell differentiation. However, our in vivo experiments demonstrated that DUSP11 deficient mice are defective in antigen-specific T cell responses and that they are more susceptible to Listeria monocytogenes infection. Using DC and T cell co-culture experiments we established that the DUSP11 signalling in DCs eventually regulates CD4 T cell activation. Together, these results demonstrate the critical role of DUSP11 in innate immunity.
A mechanistic view of the effects of manzamine A (MZA) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) (167.8)
Authors: Klosowska Karolina , Hoppe Michael , Volin Michael , Woods James 
Published: January 2023

Abstract
Previous studies suggested that MZA, an alkaloid extracted from a marine sponge, has anti-inflammatory properties which may act via mitogen-activated protein (MAP) kinases. We hypothesized that MZA would decrease phosphorylation of MAP kinases in RA FLS and reduce secretion of proinflammatory cytokines from RA synovial tissue (ST) explants. RA FLS were treated with 10 μM MZA or DMSO (vehicle) for 1 hour prior to stimulation with various dilutions of RA synovial fluid (SF) for 5 minutes and Western blotting was performed on cell lysates. Western blotting with phospho-specific antibodies demonstrated that RA SF increases the phosphorylation of the MAP kinases ERK 1/2 and JNK in RA FLS at dilutions of 1:10 and 1:25. However, pretreatment with MZA did not consistently alter RA SF-stimulated RA FLS phosphorylation of ERK 1/2 or JNK. RA ST explants were incubated with either DMSO or MZA (10, 1.0 or 0.1 µM) and conditioned media (CM) was collected after 24 hours for analysis by ELISA. CM collected 24 hrs after treatment of RA ST explants with MZA or vehicle revealed no significant differences in secretion of RANTES (CCL5) or interleukin (IL)-10. We conclude that RA SF dilutions can be used as a biologically relevant stimulant of RA FLS MAP kinase phosphorylation. We have also shown that MZA has no consistent effect on the phosphorylation of the MAP kinases ERK 1/2 or JNK. We also note that MZA may not alter secretion of IL-10 or RANTES using a RA ST explant model.
Phenotypic and epigenetic approach evaluating human M1 and M2 macrophages (167.9)
Authors: Kittan Nicolai , Allen Ronald , Hogaboam Cory , Kunkel Steven 
Published: January 2023

Abstract
Macrophages can be divided into a classically (M1) or alternatively activated (M2) phenotype depending on the cytokine environment. Commonly, IFNg±LPS and IL-4±IL-13 drive the M1 and M2 phenotype, respectively. In humans however, understanding of the M1/M2 paradigm is still evolving. Recent findings also suggest that the growth factors GM-CSF and M-CSF influence human macrophage development towards a M1- or M2-like phenotype. We analyzed macrophages grown from human blood monocytes under GM-CSF or M-CSF culture conditions that were treated with either IFNg ± LPS or IL-4/IL-13. Cells were analyzed for the expression of genes associated with the M1 and M2 phenotype. To further explore mechanisms defining the M1/M2 cells, superarray was performed to evaluate mRNA differences in the expression of chromatin modifying enzymes. In both GM-CSF and M-CSF cultured cells IFNg/LPS increased the expression of genes associated with M1 macrophages, e.g. CXCL10 and CCR7; while treatment with IL-4/IL-13 lead to an increase of M2 markers, Mannose Receptor and most prominent 15-Lipoxygenase. In addition, preliminary data also point to an involvement of histone modifying enzymes including MLL and KDM6B in the M1setting, whereas there was an association of DNA methyltransferase(s) like DNMT1 with the M2 phenotype. Overall, further analysis of the epigenetic mechanisms governing the M1/M2 phenotype will hopefully provide a better understanding of this important macrophage fate decision.
The roles of combination of dextran with gp120 on human macrophage immune response in HIV infection (168.16)
Authors: Wen Jianjun , Pang Lan , Estes Don 
Published: January 2023

Abstract
In this study, high molecular weight dextran only or combination with gp120 was used to stimulate human monocyte-derived macrophages to study the immune response to treatments and to elucidate the preliminary possibly related pathways. Our data demonstrated that 40 µg/ml of dextran did not induce a significant alteration of important immune-related gene expressions but decreased the gene expressions of CXCR4 and CCR5 mediated with reactive oxygen stress (ROS) generated by mitochondria. Cell viability measured by flow cytometry indicated that HIV induced 84% of macrophage deaths but combination of dextran with gp120 restored 48% of the mortality rate. Interestingly, a combination of dextran with gp120 can improve the enhancement of CD244 and perforin expressions induced by HIV, indicating that HIV infection is mediated to cytotoxicity. In addition, PI13 K and NFκB pathway played a very important role in the HIV-infected cell viability and ROS generation had partially influenced the cell viability. Regarding Toll-like receptors, dextran stimulated TLR1 increase, TLR9 decrease via PI13K pathway; however the alterations were restored by HIV-1 gp 120. Our data also showed that PI13K, mitochondrial ETC and NFκB pathways play very key roles in regulating perforin, CD244 and CD260. In conclusion, combination of dextran with gp120 is a good conjugate of polysaccharides to develop an HIV vaccine.
An investigation for IL-6 responses in patients with pandemic influenza A (H1N1) infection (168.20)
Authors: Bagriacik Emin , Albayrak Nurhan , Altas Basak , Ertek Mustafa 
Published: January 2023

Abstract
The pandemic H1N1 or the swine flu virus infected many people in 2009, and contributed an important morbidity and mortality around the world. Unfortunately very few markers related to the prognosis during the course of the disease have been reported so far. The purpose of this study is to investigate serum levels of IL-6 for prognosis evaluation of H1N1. A total of 29 sera from 18 patients that were confirmed to be positive for H1N1 by real time PCR in The National Influenza Center in Turkey were studied for determination of IL-6 levels using ELISA. Two groups of serum specimens collected at different time points were evaluated. The first group was collected at the acute phase of the viral infection (0-7th days) while the second group was collected at the late phase (10-20th days). Only one patient with respiratory failure died. We found a dramatic difference (p&lt;0.05) in levels of serum IL-6 between the early and the late phases of the infection. We also compared the serum IL-6 levels with the clinical symptoms obtained from patients who had a previous asthma history. The asthma patients and a patient with respiratory failure had significantly high levels (p&lt; 0.05) of IL-6 during the course of the disease. These results indicated that serum levels of a pleiotropic cytokine IL-6 might be an important marker for prognosis of H1N1 infections.
Impaired recruitment of inflammatory cells to aged lungs following influenza infection contributes to delayed virus clearance (168.24)
Authors: Eaton Sheri , Lanthier Paula , Tighe Michael , Jelley-Gibbs Dawn , Haynes Laura 
Published: January 2023

Abstract
Elderly people are very susceptible to influenza virus and often exhibit complications following infection including secondary bacterial infections and exacerbation of lung diseases. Using mouse models, it has been well established that, much like humans, aged animals exhibit a delay in clearing sublethal influenza virus infection compared to young. However, the mechanisms responsible for this delay are not well understood. In this study, we have determined that following influenza infection, the levels of early IFNg production (days 3-6) are significantly lower in aged lungs. Reduced IFNg levels lead to the reduced production of important IFNg-dependent chemokines by innate lung cells, including CCL3, CCL4 and CXCL10, which are necessary for the proper recruitment of inflammatory cells such as neutrophils. This observation is important since it is now appreciated that neutrophils are critical for efficient viral clearance. Reduced lung neutrophil numbers and reduced lung immunopathology were observed in aged flu-infected animals, indicating an overall less vigorous immune response. This diminished initial response plays an important role in the delay in virus clearance. In addition, it also subsequently contributes to lingering inflammation in aged lungs, including high levels of inflammatory cytokines and chemokines, which can contribute to exacerbating pre-existing lung disease.
Guanylate binding protein (GBP) 4 negatively regulates virus induced type I interferon and antiviral response by targeting interferon regulatory factor (IRF) 7 (168.30)
Authors: Sun Bing , Wang Jie 
Published: January 2023

Abstract
In this study, we identify GBP4 as a virus-induced protein interacting with IRF7, which is the master regulator in virus triggered induction of type I IFNs. Overexpression of GBP4 inhibits virus triggered activation of IRF7 dependent signaling, but has no effect on NF-kB signaling, whereas the knockdown of GBP4 has opposite effects. Consistently, the supernatant from sendai virus (SeV) infected cells in which GBP4 has been silenced inhibits the replication of vesicular stomatitis virus (VSV) more efficiently. Competitive coimmunoprecipitation experiments indicate that GBP4 disrupts the interactions between TRAF6 and IRF7, resulting in the impaired virus induced IRF7 phosphorylation. Collectively, our results suggest that GBP4 is a negative regulator of virus triggered type I interferon production, and it is identified as a novel protein targeting IRF7 and inhibiting its function.
The susceptibility of mice suffered from burn and irradiation injuries to pseudomonal wound infections (169.11)
Authors: Nakamura Kiwamu , Okita Yamato , Cornforth Michael , Herndon David , Kobayashi Makiko , Suzuki Fujio 
Published: January 2023

Abstract
In huge nuclear power plant accidents, victims suffered from injuries combined with burn and irradiation have been reported. In this study, the susceptibility of these victims to infection with P. aeruginosa was studied in a mouse model. One day after 3-5 Gy of whole body 137Cs γ-irradiation, mice were exposed to 5% total body surface area flame burn. These mice were subcutaneously infected with 50 CFU/mouse of P. aeruginosa surrounding the burn site. The susceptibility of mice with combined injuries to the infection was evaluated by (i) mortality rates and (ii) growth of the pathogen in various organs. In the results, all mice with combined injuries died within 3 days of infection, while all groups of control mice (normal, burned, and irradiated mice) survived. Higher numbers of bacteria were observed in organs of mice with combined injuries. The numbers of CD49b(+)/TCR(−) cells greatly increased in the spleens of mice with combined injuries, as compared with those of 3 other controls (23.7%, mice with combined injury; 2.7%, normal mice; 11.6%, burned mice; 12.5%, irradiated mice). CD49b(+)/TCR(−) cells demonstrated in mice with combined injuries inhibited the bactericidal activity of macrophages. These results suggest that CD49b(+)/TCR(−) cells may play a role on the increased susceptibility of mice to P. aeruginosa burn wound infection.
Engagement of Heterogeneous Nuclear Ribonucleoprotein M with Listeriolysin O Induces Type I Interferon Expression and Restricts Listeria Monocytogenes Growth in Host Cells (169.12)
Authors: Zheng Shijun , Luo Zheng , Li Zhonghua , Chen Kun , Li Xiaoqi , Cao Hong 
Published: January 2023

Abstract
Listeriolysin O (LLO) is a key virulence factor secreted by the Gram-positive, facultative intracellular pathogen Listeria monocytogenes (LM). Its role in host cell response is still not very clear. Using pull-down assay, mass spectrometry analysis and immunoprecipitation approaches, we found that LLO interacted with heterogeneous nuclear ribonucleoprotein M (hnRNP M), a member of RNA splicing complex apparatus, and the binding domain of LLO for hnRNP M was located between amino acids 26-176. Knockdown of hnRNP M inhibited LLO-induced activation of IFN-α, IFN-β and AP-1 promoters and enhanced LM growth in host cells. Thus, engagement of hnRNP M with LLO induces type I interferon expression and restricts LM growth in host cells, suggesting a critical role of hnRNP M in LLO-induced immune responses in host cells. These findings will contribute to further understandings of the molecular mechanisms underlying the host defense against LM infection.