Suppression of Alkali Burn-Induced Corneal Neovascularization by Dendritic Cell Vaccination Targeting VEGF Receptor 2

Mochimaru, Hiroshi; Usui, Tomohiro; Yaguchi, Tomonori; Nagahama, Yasuharu; Hasegawa, Go; Usui, Yoshihiko; Shimmura, Shigeto; Tsubota, Kazuo; Amano, Shiro; Kawakami, Yutaka; Ishida, Susumu

doi:10.1167/iovs.07-1396

Cited by 16 publications

(19 citation statements)

References 41 publications

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“…The commensal NP colonization densities for STs 6A and 8 were 1 ϫ 10 4.5 to 1 ϫ 10 5.0 CFU. Intranasal administration of 50 times the TCID 50 of PR8 caused the NP density of S. pneumoniae to significantly increase by over 1.5 log units to Ͼ1 ϫ 10 6 CFU (P Ͻ 0.0001) (Fig. 1B and C), which resulted in bacterial dissemination to the lungs and blood.…”

Section: S Pneumoniae Np Bacterial Densities Correlate With Invasivementioning

confidence: 97%

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Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Khan

Pichichero

2017

Infect Immun

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An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S. pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouseadapted H1N1 influenza A virus (PR/8/34). S. pneumoniae established effective commensal colonization, and influenza virus coinfection caused S. pneumoniae NP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction of S. pneumoniae NP density (Ͼ2.5 log units) than PhtD vaccination (ϳ1-log-unit reduction). However, no significant difference was observed with regard to the prevention of S. pneumoniae bacteremia, and there was no difference in mortality. Depletion of CD4 ϩ T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4 ϩ T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4 ϩ T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasive S. pneumoniae pathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

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Section: S Pneumoniae Np Bacterial Densities Correlate With Invasivementioning

confidence: 97%

“…A range of intranasal mouse-adapted H1N1 influenza virus strain PR/8/34 (PR8) inocula (50 times the 50% tissue culture infective dose [TCID 50 ] to 5 times the TCID 50 ) were administered to ST 6A-or ST 8-colonized adult mice as outlined in Fig. 1A.…”

Section: S Pneumoniae Np Bacterial Densities Correlate With Invasivementioning

confidence: 99%

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Khan

Pichichero

2017

Infect Immun

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“…One day before immunization, mice were injected i.p. with anti-CD4 mAb 400 mg/body (concentration, 2 mg/ml) and anti-CD8 mAb 5 mg/kg (concentration, 1 mg/ml), respectively (36,37). According to the results from the pilot depletion study, anti-CD4 or anti-CD8 mAbs were injected every second or fifth day, respectively.…”

Section: In Vivo Cell Depletionmentioning

confidence: 99%

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

Iwata

Bieber

Tiburzy

et al. 2013

The Journal of Immunology

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In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients’ sera recognize the noncollagenous domain 1, including the von Willebrand factor A–like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.

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“…Studies have found that hypoxia is a critical cause of up-regulation of VEGF which has been considered as a key regulator of CNV following hypoxia (Chaoran et al, 2011;Li et al, 2011;Mochimaru et al, 2008). In the CNV following ocular ischemia, the involvement of VEGF is necessary.…”

Section: Discussionmentioning

confidence: 99%

Effect of tetrandrine on the expressions of hypoxia-inducible factor-1 and vascular endothelial growth factor in neovascularized cornea

Sun¹

2011

Afr. J. Pharm. Pharmacol.

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This study investigated the effect of tetrandrine on the expressions of hypoxia inducible factor1 (HIF1 ) and vascular endothelial growth factor (VEGF) in neovascularized cornea of rats following alkaline burn. A rat model corneal neovascularization (CNV) was established by alkaline burn. The expressions of HIF1 and VEGF before and after tetrandrine treatment were detected by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) and slit-lamp biomicroscopy and photography were done to observe the neovascularization. Result showed the expressions of HIF1 and VEGF in the normal cornea were very weak or even absent. Following alkaline burn, the expressions of HIF1 and VEGF were markedly increased and mainly located in the neovascularized area and in the epithelial layer. After treatment with Tetrandrine, the density of neovascularization was significantly decreased, accompanied by remarkably decreased expressions of HIF1 and VEGF in the neovascularized corneal stroma. It is concluded that tetrandrine can effectively inhibit the neovascularization following alkaline burn in rats and reduce the expressions of HIF1 and VEGF in neovascularized cornea of rats following alkaline burn.

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Suppression of Alkali Burn-Induced Corneal Neovascularization by Dendritic Cell Vaccination Targeting VEGF Receptor 2

Abstract: These results indicate the possibility of DC vaccination targeting VEGFR2 as a novel therapeutic strategy for corneal chemical injury.

Cited by 16 publications

References 41 publications

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

Effect of tetrandrine on the expressions of hypoxia-inducible factor-1 and vascular endothelial growth factor in neovascularized cornea

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