bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of diversified vertebrate immune signaling and regulation in a basal chordate (43.30)
Authors: Xu Anlong , Yuan Shaochun , Yu Cuiling , Huang Shengfeng , Chen Shangwu 
Published: January 2023

Abstract
To well understand how the cytoplamic network for immune signaling and regulation originated from and evolved among species. Our group has dedicated extensive effort to address this question by studying amphioxus immunity at basal chordate. We first characterized a novel IgSF named as VCP, which could recognize microbes and induced phosphorylation of tyrosines in its intracellular region, as a possible precursor of vertebrate IgSF in lymphocytes. We then showed that amphioxus MyD88 can be utilized by most of the vertebrate-specific TLRs leading to the activation of the NF-κB pathway, which could be negatively regulated by SARM and the duplicated TRAFs. We further found the disparate subcellular localization and signaling activities of two amphioxus FADD homologs by showing that over-expression of amphioxus FADD1 resulted in the formation of death effecter filamentous structures in the cytoplasm and the activation of NF-κB, while translocation of the FADD2 from nuclear to cytoplasm could induce apoptosis. In all, our studies not only showed the evolutionary origin of lymphocyte signaling, the conservation of NF-κB activation and the apoptosis induction, but also revealed the regulation difference of a basic innate immune pathway and the dynamic change of apoptotic network at basal chordate depending on its huge gene expansion.
Phylogenetic and developmental study of CD4, CD8α and CD8β T cell co-receptor homologs in two amphibian species, Silurana (Xenopus) tropicalis and Xenopus laevis (43.5)
Authors: Chida Asiya , Goyos Ana , Robert Jacques 
Published: January 2023

Abstract
Although CD4 and CD8 gene homologs have been identified in many jawed vertebrates, phylogeny and functional conservation of these molecules is not fully understood. We have characterized CD4, CD8α and CD8β gene homologs in two species of the subfamily Xenopodinae, S. tropicalis, whose full genome is sequenced, and X. laevis. Multiple alignments of amino acid sequences, in these two species, as in other nonmammalian species, reveal a poor conservation of the residues of CD4 and CD8α that bind to MHC class II and class I molecules, respectively, suggesting species-specific coevolution. Phylogenetic analysis indicates that all three co-receptor genes are more related to other tetrapods than to bony fish. Furthermore, developmental and cell-specific expression patterns of these genes in X. laevis are very similar to that of mammals. X. laevis CD4 is mainly expressed by peripheral non-CD8 T cells and detected in the thymus at the onset of organogenesis, 5 days post-fertilization (dpf). The CD8β gene is specifically expressed by adult CD8 positive T cells and thymocytes, and is first detected in the thymus and intestine at 6 dpf. TCRα and TCRγ transcripts are also detected at 6 dpf, before TCRβ (9 dpf). TCRγ transcripts cloned from 7dpf are fully rearranged and in frame. This suggests that T cell subsets, possibly γ/δ T cells or even α/β T cells, reside in the intestine before the onset of thymocyte differentiation, and may contribute to mucosal immunity early in development.
The residue 96Gln of chicken CD132 is critical to bind to chicken IL-2 molecule (43.9)
Authors: Gu Jianyou , Huang Zhenyu , Ruan Xizhen , Zhou Jiyong 
Published: January 2023

Abstract
The common cytokine receptor γ chain (γc) is shared by at least six cytokine receptors and plays a critical role in the regulation of immune responses. In this study, the functional domains of chicken γc (chCD132) were mapped with monoclonal antibodies (mAb), a synthetic peptide, and a phage display peptide library. One functional mAb to chCD132 was produced using recombinant rchCD132 ectodomain protein expressed in prokaryotic cells as an immunogen and used to finely map the functional domain of the chCD132 protein. The mimotope of anti-chCD132 mAb, QEHQNL, was identified by phage display. The corresponding native epitope in the chCD132 molecule, Q84E94L95Q96N97L98, was identified by peptide-competitive ELISA. Lymphocyte proliferation and inhibition assays further confirmed that the binding of chIL-279-96 to chCD132 molecule was inhibited by chCD13282-101. Site-specific mutation indicates that chCD13282-101 changed the residue Q96 lacked the ability binding to chIL-2 molecule. These findings demonstrates that chIL-279-96 and chCD13282-101 are the functional domains of the interaction between chIL-2 and chCD132 molecules, and that the residue Q96 within chCD13282-101 is the critical site for its bioactivity and chIL-2-binding.
IL-4 stimulates production of TGF-β-induced (TGFBI) mRNA and protein in T cells but not in monocytes, fibroblasts, or pulmonary epithelial cells (44.16)
Authors: Bocharov Alexander , Luzina Irina , Lockatell Virginia , Highsmith Kendrick , Atamas Sergei 
Published: January 2023

Abstract
TGFBI is an extracellular matrix and an adhesion protein produced by a variety of cell types. It is not known whether cytokines other than TGF-β may regulate TGFBI production. RT-Q-PCR and Western blotting assays revealed production of TGFBI mRNA and protein, respectively, in cultured purified primary monocytes, primary pulmonary fibroblasts, and a pulmonary epithelial cell line A549. Stimulation of these cultures with 300 ng/ml of rhIL-4 did not cause a significant change in TGFBI mRNA after 3, 6, 12, or 24 h, or in TGFBI protein after 24 or 48h, (p &gt; 0.05 in all cases, two separate cell donors tested each on two independent occasions). Primary T cell (&gt; 95% purity) cultured from 4 separate donors and tested each on at least three occasions produced basal TGFBI mRNA and protein, although at the levels 10-15 fold below those observed in other tested cell types. Stimulation of T cells or PBMC with IL-4 revealed time dependent increases in the steady-state level of TGFBI mRNA and protein, but not in TGF-β mRNA. The maximal effect of IL-4 on TGFBI mRNA (2-6 fold increase, p &lt; 0.05) was observed at 3 h and 6 h; and on TGFBI protein at 24 and 48 h of stimulation. The effect of IL-4 on TGFBI production was not attenuated by a TGF-β-blocking antibody 1D11. Thus, IL-4 induces TGFBI production in T cells in a TGF-β-independent fashion. T cells may use TGFBI as an adhesion molecule for binding to known TGFBI receptors integrins αVβ3, αVβ5, and α3β1, collagens, and fibronectin.
Matrix metalloproteases mediate migration of pulmonary T cells in response to influenza virus infection (44.7)
Authors: Baaten Bas , Deiro Mia , Bradley Linda 
Published: January 2023

Abstract
Influenza viruses cause significant annual illness and death with recurrent seasonal epidemics and sporadic devastating pandemics. The efficiency of highly pathogenic influenza viruses has been attributed to potent and aberrant inflammatory responses, which can result in severe immunopathological damage and death in humans. T cells can contribute to pulmonary damage by lysis of infected cells and the production of pro-inflammatory cytokines. Thus, migration of T cells and their effector responses in situ are crucial steps towards immunity, but could also contribute to the high morbidity and mortality associated with pathogenic strains. We show that migration of T cells to efficiently cross the lung endothelial barrier and move through the basement membrane, which is essential for their function, is regulated by matrix metalloproteases (MMPs). MMPs have the proteolytic capability to mediate cleavage of the collagen network that makes up the basement membrane. In vitro, polarized T cells express MMP2 and MMP9 activity. We demonstrate that MMP2 and MMP9 are expressed following infection and that inhibition of activity results in decreased T cell recruitment to the respiratory tract. The discovery of the roles of MMPs in T cell function during influenza virus pathogenesis could elucidate the balance between immunity and pathology and may therefore have considerable therapeutic relevance.
Impact of sickle-cell trait on humoral immunity against Plasmodium falciparum in children living in malaria endemic areas of Mali (45.10)
Authors: Miura Kazutoyo , Diakite Mahamadou , Moretz Samuel , Zhou Hong , Diouf Ababacar , Tullo Gregory , Lopera-Mesal Tatiana , Anderson Jennifer , Fairhurst Rick , Long Carole 
Published: January 2023

Abstract
Previous studies have shown that children with sickle-cell trait (heterozygosity for normal hemoglobin A and sickle hemoglobin S, genotype AS) are resistant to P. falciparum malaria when compared with AA children. Passive transfer studies have established the importance of antibodies against blood-stage parasites. However, the impact of sickle-cell trait on immunity against parasite antigens has not been extensively studied. In a longitudinal study in rural Mali, we followed 73 AS and 126 AA children for an entire 6-month transmission season. Before the transmission season, antibody titers were measured against 4 parasite blood-stage antigens (AMA1, MSP1, EBA175 and MSP2). AS children experienced significantly fewer malaria episodes than AA children. Because there is a significant effect of age on antibody titers, we stratified children in 3 age groups (3-5, 6-8 and 9-11 years). Compared to AA children aged 9-11 years, AS children showed significantly lower antibody titers to all 4 antigens. For the 6-8 years group, AS children showed significantly lower antibody titers to EBA175 and MSP2. No differences were observed between AA and AS children 3-5 years old for any antigen. These data suggest that the antibody titers against these major blood-stage antigens before transmission season are not involved in reducing the incidence of malaria in AS children. The functional activity of antibodies (i.e., in vitro parasite growth-inhibitory activity) will be also presented.
Long-term maintenance of protective memory CD8+ T cells in the absence of CD4+ T cells in mice vaccinated against Blastomyces dermatitidis (45.3)
Authors: Nanjappa Som , Heninger Erika , Wuthrich Marcel , Klein Bruce 
Published: January 2023

Abstract
CD8+- and CD4+- T cell mediated immunity is major contributing factor for defense against pathogenic fungi. Our previous studies have shown that CD8+ T cells in the absence of CD4+ T cells protected vaccinated mice from lethal challenge with Blastomyces dermatitidis. However, it has also been shown that CD4+ T-cell help is required for maintenance of memory CD8+ T cells after viral and intracellular bacterial infections. To explore the requirements for maintenance of CD8+ T cell memory against pathogenic fungi, we tested whether fungal-specific memory CD8+ T cell persist in the absence of CD4+ T cell help. Here, we show that protective CD8+ T cell memory endures without CD4+ T-cell help for at least six months after fungal vaccination in mice. Additionally, we show that type I cytokines (IFNγ and TNFα), which are requisite for mediating protection, remained intact in the memory CD8+ T cells after a recall response to a lethal pulmonary challenge in vaccinated mice. The phenotypic markers CD27, CD62L, CD122, and CD127 of memory CD8+ T cells were similar to those on CD8+ T-cells induced with helper CD4+ T cells. These findings imply that CD4+ T cell help is not required for the generation, maintenance, and recall responses of protective memory CD8+ T cells after fungal vaccination. Our studies have potential implications for the usage of fungal vaccines in immune-compromised hosts.
A Unique Population of Tissue-Memory CD4+ T cells in the Airways after Influenza Infection that is Dependent on the Integrin VLA-1 (45.8)
Authors: Topham David , Chapman Timothy 
Published: January 2023

Abstract
During the immune response to influenza infection, activated T cells are distributed to both lymphoid and extralymphoid tissues, including the infected airways where direct recognition of viral antigen-bearing cells takes place. The collagen binding α1β1 integrin VLA-1 is essential for the development of memory CD8+ T cells in the airways but while expressed by some CD4+ T cells, its significance has not been demonstrated. We investigated the role of VLA-1 on virus-specific CD4+ T cells during and after primary or secondary influenza infection of mice. The proportion of CD4+ cells expressing CD49a (α1 integrin) was low in all tissues sampled during primary infection, but increased in the airways after viral clearance. Furthermore, during the first 24hr of a secondary influenza challenge, the majority of IFN-γ secreting effector CD4+ T cells from the airways were in the CD49a+ population. Airway CD49a+ CD4+ cells also expressed reduced markers of apoptosis compared to CD49a- cells, and fewer memory or effector CD4+ cells could be recovered from airways of α1-/- mice, though lymphoid tissues appeared unaffected. These data suggest VLA-1 expression defines a population of tissue-memory CD4+ T cells that act as rapid effectors upon re-infection, and VLA-1 expression is integral to their accumulation in the airways.
Generation of intestinal effector and memory CD8 T cells following oral Listeria monocytogenes infection (46.1)
Authors: Sheridan Brian , Jellison Evan , Lefrançois Leo 
Published: January 2023

Abstract
The intestinal mucosa contains unique inductive and effector sites designed for antigen presentation and promotion of primary and memory CD8 T cell responses. Thus, generation of adaptive immunity within these tissues likely results in T cell responses with distinct cellular outcomes. Here, we utilized an oral Listeria monocytogenes (LM) infection model in which internalin A is modified to promote invasion of murine intestinal epithelial cells. Oral infection induced a robust CD8 T cell response. In peripheral nonmucosal tissues, the majority of LM-specific CD8 T cells resemble short-lived effector cells (SLEC; CD127- KLRG1+). Surprisingly, the majority of effector CD8 T cells in the intestinal mucosa resembled memory precursor effector cells (MPEC; CD127+ KLRG1-) following oral infection. Splenectomy failed to impact the mucosal or systemic T cell response suggesting an intestinal tissue as the major site of T cell priming. Of the inductive sites examined, only Peyer’s patch (PP) LM-specific CD8 T cells expressed CD69 and CD103. Moreover, expression of these receptors was maintained on memory CD8 T cells from the PP where they reside along the border of the T cell and B cell zones. Contrary to systemic recall via i.v. infection, oral recall resulted in preferential expansion of CD8 T cells expressing both CD127 and KLRG1. The maintenance of a stable memory population uniquely tailored to respond to intestinal pathogens may be a hallmark of oral challenge.
Co-delivery of genetic adjuvants enhances mucosal immune responses induced by PMED DNA vaccination (46.15)
Authors: Franchini Anthony , Reinhart Todd , Stagnar Cristy , Narendran Amithi , Fuller Deborah 
Published: January 2023

Abstract
Mucosal immune responses play a vital role in protecting against natural influenza infection. We have shown that particle mediated epidermal delivery (PMED) of a DNA vaccine induces systemic and mucosal immune responses. PMED results in the direct transfection of epidermal cells, including skin-resident Langerhans cells (LC) to induce an immune response. Inclusion of a DNA plasmid expressing the heat-labile enterotoxin (LT) of E. coli improves systemic immune responses. We hypothesize that LT and other genetic adjuvants would similarly enhance the mucosal immunogenicity of PMED DNA vaccines. In this study, we assessed the ability of LT and the chemokine CCL20, which is involved in attracting dendritic cells and influencing T cell trafficking to the mucosa, for the ability to enhance systemic and lung immune responses. Mice were vaccinated with a influenza A nucleoprotein (NP) plasmid with or without LT and/or CCL20 as a genetic adjuvants. LT, not CCL20, enhanced IFNγ T cell responses in the lung. Th1/Th2/Th17 responses measured by ELISA showed PMED DNA vaccination induced broad T cell responses differently modulated by the adjuvants. Only LT enhanced antibody responses measured by HAI and ELISA in the lung and periphery. Enhanced adjuvant activity was correlated to higher frequency of activated APC (MHCII+/CD80+) in the draining lymph node. These data show LT as an effective genetic adjuvant for enhancing mucosal responses in the lung by modulating APC activation.
Eimeria maxima recombinant Gam82 gametocyte antigen vaccine protects against coccidiosis and augments humoral and cell-mediated immunity (46.19)
Authors: Lillehoj H. , Jang S. , Lee S. , Lee K. , Park M. , Subramanian B. , Sriraman R. , Srinivasan V. , Lillehoj E. 
Published: January 2023

Abstract
Intestinal infection with Eimeria, the etiologic agent of avian coccidiosis, stimulates protective immunity to subsequent colonization by the homologous parasite, whilst cross-protection against heterologous species is poor. This study was designed to assess a purified recombinant protein from E. maxima gametocytes (Gam82) in stimulating immunity against experimental infection with live parasites. Following Gam82 intramuscular immunization and oral parasite challenge, body weight gain, fecal oocyst output, gut lesions, serum antibody response, cytokine production, and lymphoproliferation were assessed to evaluate vaccination efficacy. Animals vaccinated with Gam82 and challenged with E. maxima showed lower oocyst shedding and reduced intestinal pathology compared with non-vaccinated and parasite-challenged animals. Gam82 vaccination also stimulated the production of antigen-specific serum antibodies, induced greater levels of IL-2 and IL-15 mRNAs, and increased splenic lymphoproliferation compared with non-vaccinated controls. These results demonstrate that the Gam82 recombinant protein protects against coccidiosis and augments humoral and cell-mediated immunity.
A role for macrophage IκB kinase in the mucosal adjuvant activity of edema toxin for sublingual vaccines (46.2)
Authors: Jee Junbae , Steiner Haley , Bonnegarde Astrid , Fial Michael , Boyaka Prosper 
Published: January 2023

Abstract
It has been demonstrated that nuclear factor κB (NF-κB) activation by IκB kinase (Ikk)β deletion in macrophages increases pro-inflammatory cytokines responses and enhances pathogen clearance. To address whether this pathway also regulates the mucosal adjuvant activity of edema toxin (EdTx), LysMcre x Ikkβf/f (IkkβΔMø) mice with Ikkβ-deleted macrophages were sublingually immunized with 50µg of Yersinia pestis F1V fusion protein with or without 15µg of EdTx as an adjuvant. Both control and IkkβΔMø mice immunized with F1V+EdTx developed higher levels of serum Abs, i.e., IgG, IgG1, IgG2a and IgA, when compared to mice immunized with F1V alone. The IkkβΔMø mice exhibited higher serum IgG2a levels (and IgG2a:IgG1 ratio) than control counterpart immunized with F1V+EdTx, suggesting that immune responses to F1V are biased toward Th1-type. These mice also showed elevated levels of F1V-specific serum IgA Abs than control littermates. The effect of Ikkβ deletion was more pronounced in secretory Abs since EdTx as adjuvant promoted higher fecal IgA Abs, as well as IgG and IgA Ab titers in saliva and vaginal washes of IkkβΔMø mice. These studies reveal a new role for macrophages and NF-κB in shaping mucosal immune responses induced by EdTx derivative adjuvants via the sublingual mucosa.
Modulation of trafficking receptor imprinting on T cells during Bordetella pertussis infection (46.7)
Authors: Abramson Tzvia , Waheed Sana , Kwong Brian , Tarlton Nicole , Ravindra Dipti , Green Caroline 
Published: January 2023

Abstract
Despite widespread vaccination against Bordetella pertussis (Bp), whooping cough is reemerging. Trafficking receptors (TR) direct cell migration to infection sites, generating protective immunity. To test our hypothesis that pertussis toxin (PTX) modifies dendritic cell (DC) imprinting of TR on T cells, leading to compromised homing to respiratory mucosa, we established a murine model for Bp and B. parapertussis (Bpp)-a strain that lacks PTX and analyzed TR expression by FACS on memory CD4+ CD44+ cells in blood vs lungs during peak infection and recovery (days 5 and 25). While blood memory CD4 cells from Bpp infection revealed 40-100% increased expression of β7, β1, α4, α1, α6, CCR6, CCR5 and CXCR3 at 5 days post infection, while cells from Bp had reduced levels of most TR and expressed α4 and β1 only later at 25 days post infection. However, expression of β7, α4, β1 and CCR6 was elevated in lung memory T cells from Bp infected mice at 5 and 25 days post infection, suggesting a local up-regulation of these molecules. In-vitro co-cultures of lung DC from 25 day post infection with Bp but not Bpp resulted in a significant imprinting of α6, CD103, α4, β1, CCR6, CD106 and LFA-1. In conclusion, TR imprinting on blood memory T cells is compromised at early Bp infection, however imprinting of TR by DC is efficient at later phase of infection supporting the prolonged manifestation of the natural disease.
Helicobacter felis-associated gastric pathology in gnotobiotic mice (46.8)
Authors: Durham Carolyn , Schmitz Julia , Schoeb Trenton , Soltau Thomas , Wolf Kyle , McCracken Vance , Lorenz Robin 
Published: January 2023

Abstract
Human gastric infection with Helicobacter pylori is associated with pathologic consequences, such as gastritis, dysplasia, and adenocarcinoma. This led to the classification of H. pylori as a type-1 carcinogen, but the role of additional non-helicobacter factors in the disease is unclear. In this study we utilized three models in C57BL/6(B6) mice to evaluate the role of gastric microbiota in H. felis disease development: germfree/gnotobiotic(B6.GB), colonized with Altered Schaedler Flora®(B6.ASF), and specific pathogen free model(B6.SPF). Despite similar histological changes over 24 weeks of infection, bacterial colonization of the three groups was different. While B6.GB and B6.ASF mice did not eradicate the helicobacter, the B6.SPF mice cleared it and acquired Lactobacillus spp, indicating that H. felis is sufficient to cause a dysplastic phenotype but alone is not causing histological damage seen in the B6.SPF mice. Over 24 weeks, IL-17 transcription decreased significantly in the B6.SPF and B6.ASF, whereas in B6.GB mice continued to be upregulated. Additionally, B6.SPF mice had very high IgG2c, while in the other two groups, IgG1 was dominant. This data suggests that though H. felis is sufficient to cause gastric inflammation, bacterial clearance is mediated not only by a CD4+ response, but also by other bacteria taking advantage of the gastric environment that has been established by the helicobacter infection.