bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of inflammation in collagen-induced arthritis by administration of recombinant Fcγ receptors (54.17)
Authors: Shashidharamurthy Rangaiah , Patel Jaina , Bozeman Erica , Selvaraj Periasamy 
Published: January 2023

Abstract
Recently we have shown that immune-complex mediated inflammation can be blocked by recombinant dimeric FcγR-Ig molecules in a mouse Arthus reaction model. In the present study, we have investigated whether administration of FcγR-Ig would inhibit the antibody-mediated hemolytic anemia, thrombocytopenia and arthritis in a mouse model. Systemic Administration of recombinant dimeric low affinity FcγRs such as human CD32A alleles (hCD32AR-Ig and hCD32AH-Ig) did not inhibit or prevent the antibody-induced hemolytic anemia and thrombocytopenia. Interestingly, we observed that after 48 hr of administration both hCD32AR-Ig and hCD32AH-Ig were able to inhibit 27% and 42% of the arthritic inflammation respectively, whereas the combination of hCD32AR-Ig and hCD32AH-Ig was able to inhibit 52% of arthritic inflammation. The severity of arthritis as assessed by inflammation and swelling in each digit and paw was significantly reduced. A single dose of hCD32A-Ig molecules was able to reduce the severity of arthritis up to 4 days, after which the disease returned and reached the maximum severity by day 7. The relapse of arthritis might be due to other mechanisms such as complement pathways or accelerated clearance of administered FcγR-Igs in arthritis mice. In conclusion, soluble dimeric FcγR-Igs could be of potential use in treating antibody-mediated autoimmune diseases such as arthritis but not for autoimmune diseases which affect blood cells such as hemolytic anemia and thrombocytopenia
In vivo regulation of IL-13 induced γδ T cell inflammatory responses by IL-17 (55.10)
Authors: Kinyanjui Margaret , Shan Jichuan , Fixman Elizabeth 
Published: January 2023

Abstract
The Th2 cytokine IL-13 regulates several aspects of asthma including airway inflammation, airway hyperresponsiveness (AHR) and mucus production. The Th17 cytokine, IL-17 is also known to participate in allergic disease since higher levels of IL-17 are associated with neutrophilia, particularly in severe or fatal asthma. To better understand the interaction of these cytokines in vivo, we intranasally administered recombinant IL-13 and/or IL-17 to anaesthetized mice. Administration of IL-13 alone led to an increase in airway inflammation and AHR. Intracellular cytokine staining of the recovered bronchoalveolar lavage cells revealed increased numbers of IL-17 producing T cells (both γδ and CD4). Administration of IL-17 alone had no effect on these experimental outcomes but did increase levels of tyrosine phosphorylated STAT3 in the lungs compared to saline controls. Treatment with both IL-13 and IL-17 led to an increase in the number of infiltrating eosinophils. While co-administration of IL-17 (with IL-13) had no effect on the number of infiltrating IL-17+ve CD4 cells, it decreased the number of IL-17+ve γδ T cells in the bronchoalveolar lavage. IL-17 also inhibited IL-13-induced increases in mRNA encoding IL-17, TGF beta and IL-6. Further studies examining the mechanism by which γδ T cells and IL-17 associated mediators are regulated by IL-13 and IL-17 are under way.
The effect of bee venom on ovalbumin-induced asthma model (55.13)
Authors: Park Soojin , Kim Jinju , Shin Minkyu , Hong Moochang , Bae Hyunsu 
Published: January 2023

Abstract
Asthma is a chronic disease marked by airway hyperreactivity and inflammation. Bee venom(BV) has been traditionally used in oriental medicine to relieve pain and to treat chronic inflammatory diseases. Some recent reports suggest that BV maybe an effective treatment for patients with asthma. However, there are still some unanswered questions relating to efficacy of BV therapy in asthma. The CD4+CD25+Foxp3+ regulatory T cell(Treg) play an important role in regulating the immune response. Treg can reduce inflammation and allergic reactions through its inhibitory functions. In this study, we reasoned that BV inhibits inflammatory diseases by effect on Treg and examined the effect of BV in naïve mice. Diverse concentration was treated everyday for 5days and BV significantly expanded Treg on 1mg/kg concentration. This result proposes that BV can attenuate asthma. We used 7-10 weeks female Balb/c mice were sensitized with ovalbumin(OVA). As a result, BV decreased inflammatory cytokine secretion including IL-4, IL-5, IL-13 in bronchoalveolar lavage(BAL) fluid. Also BV was significantly decrease structural remodeling of the airway. The number of Neutrophil, Lymphocyte, Macrophage, and total cells were significantly lower in the BV group than the OVA group. These results suggest that BV has potential therapeutic value for controlling asthma responses resulting from exposure to allergens.
Fullerene C70 derivatives inhibit mast cell mediated airway inflammation and bronchoconstriction associated with allergic asthma (55.2)
Authors: Norton Sarah , Dellinger Anthony , Zhou Zhiguo , Conrad Daniel , Kepley Christopher 
Published: January 2023

Abstract
Fullerenes are carbon nanospheres that can be solublized by the addition of polar chemical groups to the carbon cage. Tetragylocolate (TGA) is a derivatized fullerene compound that has been shown to stabilize mast cell (MC) responses in vitro (Clin Trans Sci. Vol: 1-11), thus we hypothesized it may have an effect on MC-driven diseases such as asthma. To observe the effects of TGA on chronic features of asthma in vivo, we utilized a MC-dependent model of asthma pathogenesis. Mice were sensitized by intraperitoneal injection of ovalbumin (OVA) in saline, challenged intranasally (i.n.) with OVA, and one of two treatment strategies was pursued. In one, TGA was given i.n. throughout disease development. In the other, TGA was given following an initial set of challenges to allow disease to develop prior to treatment; mice were then re-challenged with OVA to assess the effect on established disease. Mice did not exhibit any acute toxicity and liver and kidney function were normal. We find that TGA treatment significantly reduces airway inflammation and eosinophilia and dramatically reduces bronchoconstriction in either model. This may be due in part to significant reductions in IL-4 and IL-5 levels in the lungs. Studies utilizing fluorescently labeled TGA show this compound localized within mast cells in murine lung tissue, suggesting in vivo mast cell inhibition. Studies are in progress to determine in vivo effects of TGA on mast cell expression of asthma related genes.
Immunocomplexes down-modulate the induction of food allergy in mouse through CD32b- and IL-21-dependent mechanisms. (55.7)
Authors: Araujo Claudia , Ganeshan Kirthana , Bryce Paul , Sperling Anne 
Published: January 2023

Abstract
Food allergy is an adverse Th2 response whose incidence has been increasing dramatically. Previously, we have demonstrated that immunocomplexes(IC) decrease the food allergic responses. Thus, we hypothesize that inhibitory FcR is triggered by IC in food allergy. Here we investigated the contribution of CD32b signaling in the down-modulatory effect of IC in a mouse food allergy model. Wild type(WT) or CD16-/- or CD64-/- or CD32b-/- or IL-21R-/-mice were sensitized by gavage for 8 weeks with SEB, SEB+OVA or SEB+OVA-IC and challenged on the 9th week with OVA. We demonstrated that OVA-IC-sensitized WT, CD16-/- or CD64-/- mice produced lower levels of serum IgE, IL-4, IL-5, and have decreased blood eosinophilia compared to OVA group. In contrast, OVA-IC-sensitized CD32b-/- mice did present food allergic responses similar to OVA group. In addition, IL-21 levels were high in OVA-IC-sensitized WT, CD16-/-, CD64-/- mice, but in CD32-/- mice, in comparison to OVA group. Besides, OVA-IC-sensitized IL-21R-/- mice restored the food allergic responses, similar to OVA group. In conclusion, IC down-regulates the food allergic response in WT, CD16-/-, CD64-/- mice but in CD32b-/- indicating that CD32b plays a role in the down-modulatory effect of IC. Besides, IC stimulate the production of IL-21 and up-regulate food allergic responses in IL-21R-/- mice, suggesting that down-modulation induced by IC is mediated by IL-21-dependent mechanism.
Absence of the Type I IL-4 Receptor reduces IFNγ production and increases the severity of airway inflammation in an ovalbumin induced model of asthma (55.8)
Authors: Dasgupta Preeta , Smith Elizabeth , Keegan Achsah 
Published: January 2023

Abstract
The TH2 cytokines, IL-4 and IL-13, play critical roles in inducing allergic lung inflammation and also drive alternative activation of macrophages (AAM). Although both cytokines share receptor subunits and signaling proteins, there is evidence that IL-4 and IL-13 have differential roles in asthma pathogenesis. While important in TH2 differentiation, the contribution of IL-4 signaling via the Type I receptor, in modulating airway inflammation remains unclear. Here, we adoptively transferred wild-type ova primed CD4+ T cells into C57BL/6, Rag2KO, or gamma c (γc) KO mice. γcKO mice developed increased peribronchial and perivascular inflammation in the lungs upon ova challenge, compared to WT and Rag2KO mice. Moreover, significantly higher numbers of eosinophils were present in the bronchoalveolar lavage (BAL) and lung tissue in γcKO mice. Characteristic AAM proteins FIZZ1 and YM1 were expressed in lung epithelial cells in both mouse strains, but greater intensity of YM1 expression was observed in γcKOs. The number of FIZZ1+ or YM1+ airways was also significantly higher in these mice. It is known that γcKO mice lack NK cells; Type I R signaling in NK cells induces IFNγ production. Indeed, we found reduced secretion of IFNγ in the BAL in γcKO mice as compared to Rag2KO mice. These results suggest that the Type I R acts to suppress allergic lung inflammation through IFNγ production and, in the presence of TH2 effectors, the Type II R can mediate allergic responses in its absence.
Inhibitory effects of 6-(phenylsulfonyl)nicotinonitrile against Vibrio vulnificus infection to host (56.16)
Authors: Kim Myun Soo , Lim Dong Yeol , Choi Sang Ho , Kim Tae Sung 
Published: January 2023

Abstract
Vibrio vulnificus is a gram-negative bacterium that is present in marine environment, and infection of the bacteria shows rapid pathological progress. V. vulnificus induces the fever, septic shock, the formation of secondary lesions, accompanied in many cases by ulcer and edema on the patients. Mortality of primary septicemia exceeds 50 % in septic patients. In this study, we examined the antimicrobial activity of 6-(phenylsulfonyl)nicotinonitrile, named U262, against V. vulnificus in vitro and in vivo. Treatment with U262 significantly inhibited the V. vulnificus-induced cytotoxicity in human intestinal epithelial INT-407 cells. U262 itself was not toxic to host cells, and did not affect the growth of the bacteria. Interestingly, U262 treatment significantly decreased the attachment of V. vulnificus to the INT-407 cells. Furthermore, the administration of U262 increased the survival period of V. vulnificus-infected mice. The numbers of viable V. vulnificus in the small intestine, liver, spleen and blood were significantly lower in the U262-treated mice, compared with those of the untreated mice. Taken together, these results demonstrate that U262 suppresses the V. vulnificus-mediated cytotoxicity in human intestinal epithelial cells, maybe via the down-regulation of bacterial attachment to the epithelial cells, and suggest that U262 can be utilized as a novel candidate in the treatment of V. vulnificus infection.
Lung macrophages control malaria-induced pulmonary inflammation (56.17)
Authors: Lagasse H.A. Daniel , Scott Alan 
Published: January 2023

Abstract
Pulmonary edema and acute respiratory distress are archetypal symptoms of severe malaria that occur in ~20% of patients and are associated with mortality rates exceeding 70%. Little is known about the pathogenesis of lung pathology associated with Plasmodium infections. We tested the hypothesis that two major cellular populations - CD11c+CD11b- resident macrophages and CD11b+Ly6C+ recruited monocytes/macrophages - are key players in regulating the nature and magnitude of malaria-induced pulmonary pathology. During the very early stages of Plasmodium berghei infections in mice, parasites are taken up by resident macrophages. This is associated with the transient activation of resident macrophages and the release of chemokines that recruit large numbers of CD11b+Ly6C+ blood monocytes. Flow cytometry results suggest that later in infection resident lung macrophages take on a regulatory phenotype, while the recruited monocytes undergo activation, differentiation into macrophages and are responsible for the majority of parasite clearance within the lungs. Administration of a blocking monoclonal antibody (anti-CD11b; 5C6) diminishes the homing of monocytes to the lungs, resulting in decreased parasite uptake. We propose that both myeloid populations control pulmonary inflammation through the clearance of sequestered parasites within the pulmonary microvasculature as well as the regulation of pro-inflammatory processes within the lung environment.
Borrelia burgdorferi, the spirochetal agent of Lyme disease, induces type I interferon by human immune cells via detection of DNA and TLR7-dependent recognition of RNA. (56.19)
Authors: Love Andrea , Schwartz Ira , Petzke Mary 
Published: January 2023

Abstract
Borrelia burgdorferi (Bb) is the spirochetal agent of Lyme disease, the most common tick-transmitted infection in the United States. This extracellular pathogen initiates a type I interferon (IFN) response following phagocytosis and recognition of live Bb by toll-like receptors (TLRs) 7 and 9. To identify the ligands of Bb that induce the type I IFN response in human cells, cellular components of Bb were delivered into peripheral blood mononuclear cells (PBMCs) by encapsulation with DOTAP. Type I IFN-responsive genes (MX1, OAS1, IRF7) were significantly induced by RNA, DNA, and cell lysates relative to unstimulated PBMCs (p&lt;0.05 for all). Unencapsulated lysate or lysate treated with both RNase and DNase were unable to elicit this response. In contrast, proteinase K treatment of lysate had no effect. Purified, DOTAP-encapsulated Bb DNA and RNA induced production of significant levels of IFN-α (p&lt;0.01). The IFN response to RNA was abolished with RNase treatment or by specific inhibition of TLR7 (p&lt;0.01). This demonstrates that Bb RNA is the ligand for TLR7 in human cells, contributing to IFN-α production and induction of IFN-responsive genes. These results support prior data demonstrating that the type I IFN response requires phagocytosis and is not mediated by a cell surface receptor in human cells. Taken together, these data demonstrate that RNA (via TLR7) and DNA, but not protein, are the Bb cellular components that initiate the type I IFN response in human PBMCs.
IL-10 elicited during malaria infection blunts effective immune responses to non-typhoidal Salmonella (56.32)
Authors: Mooney Jason , Butler Brian , Xavier Mariana , Chau Jennifer , George Michael , Dandekar Satya , Luckhart Shirley , Tsolis Renee 
Published: January 2023

Abstract
Co-infection of non-typhoidal Salmonella serotypes (NTS) in pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia, a major source of child mortality in Africa. Here, we use a mouse model that mimics severe anemia seen in human malaria to address mechanisms by which an underlying malaria parasite infection contributes to the increased risk of developing NTS bacteremia. Plasmodium yoelli infected red blood cells were administered intraperitoneally in CBA, B6 or B6 il10-/- mice. At peak parasitemia, Salmonella Typhimurium was administered by gavage in a streptomycin-induced colitis model. Characterization of inflammation to NTS in the cecum was assessed by histopathology, microarray and qRT-PCR. Bacterial loads in systemic tissues were followed to 4 days post infection. Our results indicate that the malaria parasite infection causes a global suppression of proinflammatory responses in the intestine, blunts the intestinal neutrophil influx normally elicited during NTS gastroenteritis and increases bacterial colonization at systemic sites. Blunting of intestinal inflammatory responses was independent of hemolytic anemia, but required induction of the immunoregulatory cytokine IL-10 by the parasites. Elimination of IL-10 activity restored intestinal inflammation in co-infected mice, and administration of recombinant IL-10 was sufficient to increase systemic colonization by S. Typhimurium in the absence of parasite infection.
Chitinase activity and a novel population of CXCR3 expressing alternatively activated macrophages in the CNS during chronic Toxoplasma gondii infection. (56.33)
Authors: Nance J. , Noor Shahani , Lane Thomas , Wilson Emma 
Published: January 2023

Abstract
During infection with Toxoplasma gondii, an IFN-γ dependent polarization of classically activated macrophages (CaM) is required to control parasite growth during the acute phase of infection. These macrophages produce high levels of cytokines such as IL-12 and TNF-α and other effector molecules such as nitric oxide that act to induce stage conversion to bradyzoites resulting in a sustained chronic infection in the brain. Cytokines such as IL-4 as well as the presence of exogenous polymers such as chitin, induce alternatively activated macrophage (AMac) phenotypes involved in tissue remodeling and wound healing responses. Here we demonstrate the presence of AMac macrophages during Toxoplasma infection at a time point associated with chronic infection and substantial tissue remodeling in the brain. This population preferentially expressed the chemokine receptor CXCR3, scavenger receptors, MMR and stabilin-1. In vivo blockade of CXCR3 and CXCL10 decreased not only T cell infiltration and resulted in an increase in parasite burden but macrophage migration to the brain was also diminished. Finally, we demonstrate chitinase activity in the Toxoplasma infected brain associated with the presence of AMac and chitin in the cyst wall. These results indicate that chitin in the parasitic cyst wall locally stimulates a population of CXCR3 expressing AMac that are required for tissue remodeling and immunity in the brain during Toxoplasma infection and inflammation.
IL-1 receptor antagonist augments antibiotic resolution of joint inflammation in a novel model of Brucella-induced osteoarthritis (56.7)
Authors: Skyberg Jerod , Thornburg Theresa , Kochetkova Irina , Layton William , Callis Gayle , Riccardi Carol , Golden Sarah , Rollins MaryClare , Pascual David 
Published: January 2023

Abstract
Infection of the joints is the most frequent localized manifestation of brucellosis, which is a common cause of infectious arthritis. However, no experimental murine model of Brucella-induced arthritis has been reported. Here we report that IFN-γ-/- mice develop joint inflammation following oral, nasal, or parenteral infection with B. abortus or B. melitensis. Joints from Brucella-infected IFN-γ-/-, but not wild-type mice, were found to contain extensive inflammatory infiltrates and debris within the joint space which co-localized with brucellae. Osteoarthritis, joint space narrowing, necrosis, soft tissue inflammation, and substantial Brucella burdens were also observed, although antibody or cytokine responses against collagen were not detected. Elevated IL-1β, but not TNF-α, IL-6, nor IL-17, was detected in the joints of Brucella-infected IFN-γ-/- mice. A six-week regimen of rifampicin effectively cleared infection and halted further progression of inflammation, although some symptoms and swelling remained. However, administration of an adenovirus expressing the IL-1receptor antagonist augmented antibiotic resolution of joint swelling by &gt;50%. These results show that the IFN-γ-/- mouse represents a useful model to study the pathogenesis of joint inflammation due to Brucella infection, and that intervention strategies targeting IL-1 can complement antibiotic treatment of Brucella-induced inflammation. Supported by USDA 2007-01612 and USDA 2009-34397-20133.
IL-10 from macrophages and granulocytes is not required for chronic disease in Leishmania mexicana infection (56.8)
Authors: Buxbaum Laurence 
Published: January 2023

Abstract
Chronic disease of mice caused by the protozoan parasite Leishmania mexicana requires IL-10 and FcγRIII. Immune complexes consisting of IgG bound to the surface of Leishmania amastigotes can induce IL-10 and suppress IL-12 production from macrophages in vitro. We have found that IgG1 and IgG2a/c can each efficiently induce IL-10 from macrophages, whereas in vivo, mice that lack IgG1 and have stronger and earlier IgG2a/c responses, are more resistant to L. mexicana infection. This calls into question the crucial role of macrophages as the source of IL-10 required for chronic disease. We now show that tissue-specific IL-10-deficient mice lacking IL-10 from macrophages and granulocytes still have chronic disease similar to WT C57BL/6 mice. These Lyz2-cre-IL-10fl/fl mice clearly lack IL-10 from macrophages as expected, but have a similar course of infection and parasite loads as the WT mice. This shows more directly that macrophage IL-10 is not required for chronic disease and that neutrophils are also not a required source of IL-10. Prior work showed that depletion of CD25+CD4+ T cells also produced no major change in chronic disease and that T cell IL-10 in lymph nodes did not differ in mice that heal (such as FcγRIII KO mice) and those that have chronic disease (WT mice). This leaves an open question as to the important source of IL-10, likely in lesions rather than in the lymph node.
Soluble IL7 receptor alpha chain serves as a depot to prevent IL7 consumption (57.1)
Authors: Lundstrom Wangko , Walsh Scott , Mackall Crystal 
Published: January 2023

Abstract
IL7 signals through a receptor comprised of IL7Ra and IL2RG. Association studies have shown IL7R genotype modulates susceptibility to MS. The MS associated allele also increases an alternatively spliced mRNA isoform encoding a soluble receptor (sIL7Ra). Thus sIL7Ra seems to be associated with increased MS risk, however the biological mechanism behind this is poorly understood. We want to determine the effect of sIL7Ra on IL7 signaling as a first step toward determining how polymorphisms in IL7R modulate risk for MS.We produced recombinant isoform encoded sIL7Ra and recombinant extracellular IL7Ra (i.e. shed IL7Ra) and measured binding to IL7 using Biacore. Both proteins show intermediate affinity binding to IL7, with sIL7Ra demonstrating 15-fold increased affinity (Kd=6.3nM) compared to extracellular IL7Ra (Kd=98nM). We measured the effect of sIL7Ra on IL7 mediated cell survival using 2E8, an IL7 dependent cell line. At day 3 sIL7Ra diminished IL7 mediated survival, however at day 9 and 12 the effect is reversed and presence of sIL7Ra increases survival compared to cells cultured with IL7 alone.In conclusion, sIL7Ra competes with membrane bound IL7Ra for IL7 binding. This initially decreases IL7 signaling, but later on IL7 is preserved in the presence of soluble receptor. We postulate that sIL7Ra serves as a depot for IL7, resulting in more persistent IL7 signal over time. Increased levels of soluble IL7Ra may increase the risk of MS by maintaining stronger IL7 signals.