bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severity of intestinal disease following Campylobacter jejuni infection correlates with level of TNF-α production and macrophage apoptosis (42.6)
Authors: Tabbara Khaled , Al Muraikhi Amal , Bazzi Ali , Botta Giuseppe 
Published: January 2023

Abstract
Campylobacter jejuni causes diarrhea ranging from mild to bloody.Penetration of epithelial barrier allows organisms to interact with macrophages inducing proinflammatory cytokines. Infection of macrophages induces apoptosis, potentially leading to immune evasion or suppression. We investigated invasiveness, cytokine production and apoptosis of the human monocytic cell line THP-1 using three human C. jejuni isolates. To determine invasiveness,THP-1 cells were infected in vitro,treated with Gentamicin, lysed and plated. Cytokine mRNA expression was determined by semi quantitative multiplex RT-PCR and protein by ELISA.Apoptosis was determined by flow cytometry following Annexin V and TUNEL staining of infected cells. In vitro invasiveness of isolates correlated with disease severity. The isolate from severest disease(3915) was most invasive and the least invasive isolate was from the patient with mildest disease(115) while the third isolate from a patient with intermediate severity(417) fell in between. Cytokine message and expression(IL-1β,TNF-α and IL-8) was highest with 3915 followed by 417 and the least being 115. Differences between the three isolates were most prominent in TNF-α where mRNA expression following 3915 infection was about 3x of 417 and about 7x of 115. ELISA showed similar differences. 60.7% of 3915 cells underwent apoptosis while 417 induced 42.3% and 115 only 30%. We suggest that severity of disease is related to levels of TNF-α production and apoptosis.
IMMUNOSUPPRESSIVE CYTOKINE PRODUCTION IN BOVINE VITAMIN A -DEFICIENT CHALLENGED WITH M. BOVIS (43.13)
Authors: Silva Ediane , Reis Michelle , Waters W Ray , Nonecke Brian , Junqueira-Kipnis Ana Paula , Estes Don Mark 
Published: January 2023

Abstract
It has been shown that vitamin A could induce T regulatory (Treg) cells, especially in the tuberculosis infection. One of action mechanism these cells are due the cytokines presence as IL-10, TGF-β and FOXP3. In this study was evaluated the production of these cytokines in vitamin A sufficient and deficient tuberculosis calves. Animals of 1 - 2 weeks old from a TB-free source were fed with a diet containing or not vitamin A. PBMC were cultivated with or without PPD, and then cells were stained for CD8, WC1γδ T and NK cells receptors for flow cytometry analysis. The cells culture supernatant was evaluated by ELISA for TGF-β. qRT-PCR assay was performed from lung and lynphonod tissues to detect the IL-10, TGF-β and FOX-P3 expression. According to our results Vitamin A supplied animals had higher number of IL10 secreting cells, especially CD8+ (2.27±1.36) and WC1γδ T (2.44±1.48) cells PPD stimulated. Vitamin A deficient animals showed higher numbers of NK+IL10+ (3.46±2.77) cells. The TGF-β in the supernatant from bovines vitamin A supplied was higher (125.15 pg/ml) than vitamin A deficient (16.5 pg/ml). The TGF-β and IL-10 mRNA expression was the same for Vitamin A supplied and deficient, in the lung as well as the lymph node. The IL10 secreting role seems to be more associated to WC1 γδ T and NK cells. Vitamin A diet influences the immunosuppressive cytokine production, especially the TGF-β, when the cells are activated.
Immunogenicity of Anaplasma marginale T4SS proteins (43.18)
Authors: Brown Wendy , Morse Kaitlyn , Sutten Eric , Norimine Junzo 
Published: January 2023

Abstract
For many bacterial pathogens, including Anaplasma marginale, outer membranes (OM) can induce protective immunity. Key questions are what outer membrane proteins are immunogenic and whether linked recognition of associated membrane proteins is important for protection. The type IV secretion system is a virulence factor comprised of approximately 12 proteins spanning the inner and outer membranes of many Gram-negative bacteria. A reverse genetic approach identified immunogenic type IV secretion system (T4SS) proteins VirB9-1, VirB9-2, and VirB10 recognized by sera and T cells of A. marginale OM vaccinated cattle. Recognition of these by sera from infected cattle suggests surface expression. Additional T4SS proteins were expressed, and recombinant VirB2, VirV7, VirB11, and VirD4 also stimulated significant T-cell responses in OM vaccinees. These proteins were not generally recognized by immune sera. Strong IgG2 responses to VirB9-1 or VirB9-2 in the absence of CD4 T cell responses in two OM vaccinees suggests that a T4SS protein partner associated with VirB9-1 provides T cell help for isotype switching. In Agrobacterium tumefaciens VirB9 associates with VirB10 and VirB7, and we have data indicating associations of both VirB9 proteins with each other and with VirB10. The use of T4SS proteins and protein complexes as immunogens to prevent or reduce infection is a novel strategy for developing vaccines for many pathogenic bacteria.
Innate and adaptive immune defenses against a fungus linked to global amphibian declines in the South African Clawed Frog, Xenopus laevis (43.24)
Authors: Ramsey Jeremy , Reinert Laura , Harper Laura , Woodhams Douglas , Rollins-Smith Louise 
Published: January 2023

Abstract
Many amphibian species have suffered population declines due to an emerging infectious disease, chytridiomycosis, caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). Little is known about immune defenses against this skin pathogen. Here we show that antimicrobial peptides in the skin mucus of the South African clawed frog, Xenopus laevis, inhibited Bd growth in vitro, and skin peptides secreted under natural conditions were within the range of concentrations required to inhibit Bd growth. Peptide secretion was induced by norepinephrine stimulation in a dose-dependent fashion. Maximal stimulation resulted in peptide depletion and increased susceptibility to infection. Frogs required approximately 28-50 days for peptide renewal. Following experimental exposure, infection intensity in the skin was greatest from 20-30 days and declined significantly by 45 days. Thus, immune defenses effectively cleared the infection by seven weeks. Sublethal X-irradiation of frogs resulted in decreased leukocyte numbers in the spleen and greater susceptibility to infection. Immunization against Bd resulted in elevated IgM and IgY antibody responses in vivo that persisted for greater than four weeks. Mucus secretions from X. laevis previously exposed to Bd five months earlier contained IgM, IgY, and IgX antibodies. These data strongly suggest that both innate and adaptive immune defenses are critical in the resistance of X. laevis to lethal Bd infections.
Evidence for somatic hypermutation at shark T cell receptor α locus (43.6)
Authors: Criscitiello Michael , Eubanks Jeannine , Coots Andrea , Flajnik Martin 
Published: January 2023

Abstract
Somatic hypermutation (SHM) is a mechanism B cells use while responding to antigen for affinity maturation, and is also employed in the diversification of the primary B cell repertoire in the gut associated lymphoid tissues of ruminants. Recently it was discovered that SHM operates at the T cell receptor γ locus of the sandbar shark. We have looked for evidence of this AID-mediated mechanism at other T cell receptor loci in the nurse shark, Ginglymostoma cirratum. Our initial hypothesis invoked SHM at the γ and δ loci, but not at the (presumably) MHC-restricted α and β loci. Surprisingly, we find evidence for mutation at the α locus. We see evidence for canonical point mutations as well as the tandem mutations that have been a hallmark of SHM at traditional immunoglobulin, IgNAR and now T cell receptor loci of cartilaginous fish. Ongoing studies are assaying SHM at α in the shark thymus to determine if this phenomenon is being employed for affinity maturation of αβ T cell responses (a process we deem unlikely with MHC restriction). Alternatively, SHM may be used along with receptor editing at the α locus in the thymus to generate primary repertoire paratopes that can mutate to positive selection. The thymus was suggested as a “mutant breeding” organ for self tolerance by Neils Jerne forty years ago - future comparative studies will determine if SHM is an original tool of vertebrate T cells for thymic diversification or an adaptation singular to sharks.
Blood dendritic cells in cardiovascular disease risk (44.13)
Authors: Carrion Julio , Zeituni Amir , Bear Adam , Cutler Christopher 
Published: January 2023

Abstract
An estimated 80 million U.S. adults have one or more types of cardiovascular diseases (CVD) with the total cost to the U.S. for 2009 estimated to be $475.3 billion. Atherosclerosis (ATH) is the single most important contributor to CVD; however, only 50% of ATH patients have currently identified risk factors. Chronic periodontitis (CP), a common inflammatory disease, is linked to an increased CVD risk. Dendritic cells (DCs) which infiltrate arterial walls and destabilize atherosclerotic plaques, have been implicated in CVD. While the source of atherogenic DCs is presently unclear, we propose that dermal DCs from peripheral inflamed sites, such as CP tissues are a source. We therefore designed a clinical study to elicit, quantitate and isolate DCs in the peripheral blood of otherwise healthy CP patients. Ten patients with CP were consented according to IRB standards and enrolled in the study. Peripheral blood collected at baseline and 24 hrs after mechanical debridement (MD) was used to identify and sort blood DCs. After PBMC separation, DCs were labeled with DC-SIGN-APC and BDCA-1-PE and quantitated by FACS analysis. We found that after MD there was a 5-6% increase in the numbers of blood DCs in this patient population. This increase in the blood may represent mobilization of DCs from bone marrow stores, as well as from CP tissues. We are presently analyzing the DC transcriptome of sorted DCs to identify markers of atherogenesis.
Thioredoxin inhibits epidermal Langerhans’ cell (LC) migration in man and mouse (44.6)
Authors: Dearman Rebecca , Cumberbatch Marie , Del Val Greg , Almond Rachael , Griffiths Christopher , Kimber Ian 
Published: January 2023

Abstract
Epidermal LC play a critical role in the initiation of skin immune responses. LC migration is dependent upon cytokine signals, provided by tumour necrosis factor-α (TNF-α) and interleukin (IL)-1β. We have now examined the ability of human recombinant thioredoxin (hTrx), a redox-active protein, to influence LC migration. Wild type hTrx and various cysteine to alanine mutants were produced in E coli. LC migration in response to chemical contact allergen (oxazolone; Ox) or to intradermal (id) injection of recombinant murine TNF-α or IL-1β was assessed in BALB/c mice. LC migration was provoked in healthy human volunteers (n=10) by id injection of recombinant human TNF-α. Various forms of hTrx were administered by topical application 2h prior to the migratory stimuli. LC densities were assessed in epidermal sheets by immunofluorescent staining for MHC class II (mouse) or CD1a (human). Topical application of hTrx inhibited significantly Ox- and TNF-α-induced LC migration in BALB/c strain mice, but failed to impact on IL-1β-induced migration. Use of mutant forms of hTrx demonstrated that this ability was redox-independent. Application to the skin of wild type hTrx to human volunteers inhibited TNF-α-induced LC migration also. Inhibition of LC migration was selective for IL-1β-dependent stimuli (contact allergen and TNF-α). These data suggest that thioredoxin possesses novel immunomodulatory properties as a result of its ability to modulate IL-1β production and/or signalling.
L-selectin expression on CD4+ T cells is critical for antibody production, whereas L-selectin expression on both CD4+ and CD8+ T cells is important for dermatitis in a mouse model of atopic dermatitis (44.9)
Authors: Kadono Takafumi , Tomota Manabu , Ohmatsu Hanako , Kai Hiromichi , Asano Yoshihide , Sugaya Makoto , Sato Shinichi 
Published: January 2023

Abstract
L-selectin is a cell adhesion molecule that plays an important role in leukocyte migration especially to peripheral lymph nodes. L-selectin deficiency is known to decrease subcutaneous immune responses, however, the role of L-selectin in atopic dermatitis model is unknown. Moreover, it is not clear on which cell subset the expression of L-selectin is critical for cutaneous inflammation. Here, we showed that in mouse atopic dermatitis model elicited by epicutaneous sensitization with ovalbumin (OVA) OVA-specific antibody production and dermatitis is completely lost with L-selectin deficiency. We also found that L-selectin expression on CD4+ T cells is critical for antibody production, whereas L-selectin expression on both CD4+ and CD8+ T cells is important for dermatitis. Moreover, as few as 100 OVA-specific CD4+ T cells were able to elicit OVA-specific antibody production in L-selectin deficient mice. When wild-type CD4+ T cells were intravenously injected to L-selectin deficient mice, OVA-specific antibody-forming cells existed mostly in draining lymph nodes, suggesting that L-selectin-positive CD4+ T cells recruited to draining lymph nodes could muster antibody-forming cells independent of L-selectin. These results suggested that this mouse atopic dermatitis model is completely L-selectin dependent with L-selectin on CD4+ T cells and CD8+ T cells playing distinctive roles, and targeting L-selectin may be an option for treating atopic dermatitis.
IL-17 is critical for the generation of protective Th1 immunity against intracellular pathogens (45.1)
Authors: Lin Yinyao , Gopal Radha , Khader Shabaana 
Published: January 2023

Abstract
The importance of T helper type 1 (Th1) cell immunity in host resistance to the intracellular pathogens is well established. However, the relative roles of Interleukin (IL)-12-Th1 and IL-23-T helper type 17 (Th17) cell responses in immunity to intracellular pathogens is not well described. The IL-23-Th17 pathway is critical for protective immunity against extracellular bacterial infections. In contrast, the IL-23-Th17 pathway is dispensable for protection against intracellular pathogens such as Mycobacterium tuberculosis and Listeria. However, our data suggest that IL-17 regulates the Th1 pathway and is required for protective immunity against some intracellular pathogens such as Francisella tularensis Live Vaccine Strain and M.bovis BCG. IL-23-dependent IL-17 induces IL-12 in myeloid cells and is required for the generation of IFNγ producing adaptive immune responses. These findings illustrate a novel biological function for IL-17 in regulating IL-12-Th1 immunity and host responses against intracellular pathogens.
Regulation of proinflammatory cytokine Interleukin-6 (IL-6) induction by NF-kappaB signaling in pandemic H1N1 influenza A virus-infected human bronchial epithelial cells (45.29)
Authors: Xing Zheng , Gao Wei , Qu Bingqian , Li Xue , Jin Yu , Yang Ku , Cardona Carol 
Published: January 2023

Abstract
The influenza A (H1N1) pandemic of 2009 is caused by a novel swine influenza virus, which has resulted in thousands of mortalities worldwide. Pulmonary failure due to over-induction of proinflammatory factors appeared to be the main cause in severe cases leading to death. To elucidate the pathogenesis of the novel H1N1 virus in humans, we infected human bronchial epithelial cells with A/Nanjing/NJU108/2009 (H1N1), isolated from a patient in Nanjing, China, and analyzed expression profiles of various cytokines and chemokines. We found that among proinflammatory cytokines, IL-6 was induced up to hundred and thousand fold after infection, while the levels of IL-1beta and IL-8 remained unchanged. This study aims to understand how NF-kappa B (NFκB) signaling pathway regulates the induction of IL-6 upon infection. Surprisingly, when a specific IKKalpha/beta inhibitor was used, IL-6 induction was not affected. IL-6 induction was, however, greatly suppressed by an NFκB1/p100 inhibitor, which indicates that the NFκB signaling was involved in the regulation of IL-6 but the classical NFkB pathway seems to be only partially implicated. We further examined the phosphorylation and activation of IKKs, NFκB1 and NFκB2, and other regulators in NFκB signaling. Our data demonstrated that a novel mechanism was employed in NFκB signaling pathway which regulates IL-6 induction and may play a critical role in pathogenesis in humans infected with the novel pandemic H1N1 influenza A virus.
Recycling endosomal membranes contribute to Toxoplasma gondii parasitophorous vacuole formation in mast cells (45.4)
Authors: Smith Norah , Butcher Barbara , Denkers Eric , Baird Barbara , Holowka David 
Published: January 2023

Abstract
For the obligate intracellular parasite, Toxoplasma gondii, elucidating its initial interactions with host cells and their parasitophorous vacuole membrane (PVM) is important for better understanding T. gondii infection. In many cell types, recycling endosomal (RE) trafficking often contributes to plasma membrane remodeling during processes such as phagocytosis. Previously, we characterized RE trafficking in RBL-2H3 mast cells and demonstrated IgE/antigen-stimulated outward trafficking of FITC-cholera toxin B (CTxB) bound to GM1 on RE membranes. When these cells are infected with virulent Type I strain tachyzoites, we find that invading parasites have an accumulation of FITC-CTxB on the PVM at early times after infection. This response is substantially enhanced when FITC-CTxB labels the RE pool in addition to the plasma membrane, providing evidence that RE membranes contribute to the nascent PVM. Consistent with earlier studies, IgE bound to its receptor at the plasma membrane shows no detectable accumulation at the PVM during this early stage (first hour) of infection. Under these conditions, antigen-stimulated degranulation is substantially inhibited, suggesting that parasitic infection interferes with normal signaling responses in these cells. Our ongoing research aims to further investigate the possible link between the PVM and RE trafficking and the potential immunomodulatory effects of T. gondii on infected mast cell signaling.
Depot versus dispersal: biodegradable polymer vaccination effects of size and chemistry (46.17)
Authors: Huntimer Lucas , Phanse Yashdeep , Petersen Latrisha , Carrillo-Conde Brenda , Ramer-Tait Amanda , Narasimhan Balaji , Wannemuehler Michael 
Published: January 2023

Abstract
Development of safe and efficacious vaccine regimen including delivery vehicles, routes, and adjuvants is paramount to public health and preventive medicine. This study evaluated the whole body distribution of unique, surface eroding polymers prepared from aliphatic sebacic acid (SA) and aromatic 1,6-bis(p-carboxyphenoxy)hexane (CPH). The inherent surface erosion kinetics permit development of a single dose vaccine based on tailored release kinetics of immunogen, adjuvanticity and sparing of protein dose, and sustained antigen presentation. Fabrication methods were used to create a size range (400 nm to 10 µm) of particles encapsulating LSS 640 fluorophore. These particles were used to evaluate in vivo distribution following intranasal (IN) or subcutaneous (SC) administration to mice. Using live animal imaging at multiple time points, fluorescent analysis at the injection and distal anatomical sites establish that microparticles distributed in a pattern consistent with a depot effect that was dependent upon the injection route. In contrast, nanoparticles distributed systemically regardless of route. Ex vivo analysis of excised tissues verified nanoparticle distribution to distal sites. The ability to assess the depot and dispersal effect of this novel delivery platform in real time consequent to the induction of an antibody response will provide insight into how size and polymer chemistry can be used therapeutically to effect targeting of a vaccine to desired immune tissues.
Novel role of galectin-4: A potent inducer of monocytes differentiation and activation. (47.12)
Authors: Hong So-Hee , Do Ji-Hye , Shin Jun-Seop , Park Chung-Gyu 
Published: January 2023

Abstract
Galectin-4 (Gal-4) is one of β-galactoside-binding proteins (Galectin family) and is specifically expressed in the gastrointestinal tracts. Although intensive studies have been done on other isoforms of Galectin (Gal-1, -3, -9), the role of Gal-4 in immune system remains unknown. Here, we found that Gal-4 specifically affects the differentiation and activation of monocytes. In addition to prolonging monocytes cell survival, Gal-4 induced morphological changes of monocytes into macrophage-like cells. Notably, Gal-4 entered into the cytoplasm of monocytes after binding and increased the production of pro-inflammatory cytokine such as IL-6 and TNF-a. Gal-4 also increased the expression of co-stimulatory molecule such as CD40, 80 and CD86 in CD14+ monocytes. Furthermore, we provide the evidence that Gal-4 mediated its modulatory function through MAPK signaling cascade (p38 and c-Jun) via MyD88 by Western blot analyses. As such, Gal-4 did not increase macrophage differentiation markers in MyD88-deficient monocytes from MyD88 knockout mice. In conclusion, our study is the first to describe the specific effect of galectin-4 on monocytes and further suggests that Gal-4 expression might modulate mucosal immunity via monocytes activation and differentiation.
A functional impairment of Foxp3+CD4+ regulatory T cell may lead to the exacerbated inflammation in ARDS. (47.2)
Authors: Elhadad Sonia , London Lucille 
Published: January 2023

Abstract
Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by an intense host inflammatory response to an infectious, non-infectious, or extrapulmonary insult. It is associated with the development of lung damage, the rapid onset of severe respiratory and organ failure. Neutrophils and lymphocytes have been shown to accumulate in the airways. However, the mechanisms that lead to this aberrant inflammation and the nature of the lymphocyte subsets involved in the recruitment of neutrophils to the lung and in their activation are not yet clearly defined. Using a unique mouse model of virus-induced ARDS that recapitulates the histopathology observed in patients with ARDS, we hypothesized, that the inflammation observed in ARDS is the result of (i) a defective regulatory Foxp3+CD4+ T cell population (T-reg), and (ii) an imbalance in the modulation of T-regs and the proinflammatory TH17 population. Therefore, we evaluated the presence of Foxp3+CD4+ T-regs in the lungs and BAL fluid of infected mice. We observed a difference in the phenotype of the regulatory T cell population in the lungs at different stages of the disease from progression to recovery in our virus-induced ARDS model. We concluded that the inflammation observed in our model, does not result from the absence of regulatory T cells, but may result from an impairment of the function of the Foxp3+CD4+ regulatory T cells, which may contribute to the uncontrolled inflammation observed in ARDS.