Author Correction: The wide utility of rabbits as models of human diseases

Esteves, Pedro J.; Abrantes, Joana; Baldauf, Hanna Mari; BenMohamed, Lbachir; Chen, Yuxing; Christensen, Neil D.; González‐Gallego, Javier; Giacani, Lorenzo; Hu, Jiafen; Kaplan, Gilla; Keppler, Oliver T.; Knight, Katherine L.; Kong, Xiangzhen; Lanning, Dennis; Pendu, Jacques Le; Matos, Ana Lemos de; Liu, Jia; Liu, Shuying; Lopes, Ana M.; Lü, Shan; Lukehart, Sheila A.; Manabe, Yukari C.; Neves, Fabiana; McFadden, Grant; Pan, Ruimin; Peng, Xuwen; Sousa-Pereira, Patrícia de; Pinheiro, Ana; Rahman, Masmudur M.; Ruvoën-Clouet, Natalie; Subbian, Selvakumar; Tuñón, María J.; Loo, W. van der; Vaine, Michael; Via, Laura E.; Wang, Shixia; Mage, Rose G.

doi:10.1038/s12276-019-0252-0

Cited by 7 publications

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“…The virus was triple plaque purified and prepared as previously described (35,39). Groups of New Zealand White rabbits and HLA Tg (8 to 10 weeks) received an ocular HSV-1 challenge (2 ϫ 10 5 PFU, McKrae strain) without scarification (28,39,59,(62)(63)(64). Following ocular infection, rabbits were monitored for ocular herpes, virus infection, and disease (28,39,59,(62)(63)(64).…”

Section: Methodsmentioning

confidence: 99%

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Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

Roy

Coulon

Prakash

et al. 2019

J Virol

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Chronic viruses such as herpes simplex virus 1 (HSV-1) evade the hosts’ immune system by inducing the exhaustion of antiviral T cells. In the present study, we found that exhausted HSV-specific CD8+ T cells, with elevated expression of programmed death ligand-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) receptors were frequent in symptomatic patients, with a history of numerous episodes of recurrent corneal herpetic disease, compared to asymptomatic patients who never had corneal herpetic disease. Subsequently, using a rabbit model of recurrent ocular herpes, we found that the combined blockade of PD-1 and LAG-3 pathways with antagonist antibodies significantly restored the function of tissue-resident antiviral CD8+ TRM cells in both the cornea and the trigeminal ganglia (TG). An increased number of functional tissue-resident HSV-specific CD8+ TRM cells in latently infected rabbits was associated with protection against recurrent herpes infection and disease. Compared to the PD-1 or LAG-3 blockade alone, the combined blockade of PD-1 and LAG-3 appeared to have a synergistic effect in generating frequent polyfunctional Ki-67+, IFN-γ+, CD107+, and CD8+ T cells. Moreover, using the human leukocyte antigen (HLA) transgenic rabbit model, we found that dual blockade of PD-1 and LAG-3 reinforced the effect of a multiepitope vaccine in boosting the frequency of HSV-1-specific CD8+ TRM cells and reducing disease severity. Thus, both the PD-1 and the LAG-3 exhaustion pathways play a fundamental role in ocular herpes T cell immunopathology and provide important immune checkpoint targets to combat ocular herpes. IMPORTANCE HSV-specific tissue-resident memory CD8+ TRM cells play a critical role in preventing virus reactivation from latently infected TG and subsequent virus shedding in tears that trigger the recurrent corneal herpetic disease. In this report, we determined how the dual blockade of PD-1 and LAG-3 immune checkpoints, combined with vaccination, improved the function of CD8+ TRM cells associated with a significant reduction in recurrent ocular herpes in HLA transgenic (Tg) rabbit model. The combined blockade of PD-1 and LAG-3 appeared to have a synergistic effect in generating frequent polyfunctional CD8+ TRM cells that infiltrated both the cornea and the TG. The preclinical findings using the established HLA Tg rabbit model of recurrent herpes highlight that blocking immune checkpoints combined with a T cell-based vaccine would provide an important strategy to combat recurrent ocular herpes in the clinic.

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Section: Methodsmentioning

confidence: 99%

“…At the end of the incubation period, the cells were transferred to a 96-well round-bottom plate and washed once with FACS buffer. Surface and intracellular staining were done as we described previously (28,39,59,(62)(63)(64). LSRII acquired a total of 50,000 events (Becton Dickinson, Mountain View, CA), followed by analysis using FlowJo software (TreeStar).…”

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confidence: 99%

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

Roy

Coulon

Prakash

et al. 2019

J Virol

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“…Rabbits are widely used in translational research for the reasons detailed below that also support their value for breast cancer research. They are phylogenetically more related to primates than rodents [6] and show similarities to humans regarding their immune system gene expressions, physiological functions and pathomorphological findings [5,6,57]. Housing and breeding are facilitated by their tame behavior, short gestation periods and average litter sizes of 4–12 pubs [5,6,8].…”

Section: Discussionmentioning

confidence: 99%

“…They also show several traits, some of which are breed- or line-specific, making them suitable models for different aspects of biomedical research [2,3]. Rabbits are models for several non-infectious and infectious human diseases [2,3,4,5,6]. These include atherosclerosis, hypertension, cataracts and Alzheimer’s disease [2,3,4,5,6], as well as syphilis, tuberculosis and viral-induced acute hepatic failure [5].…”

Section: Introductionmentioning

confidence: 99%

“…Rabbits are models for several non-infectious and infectious human diseases [2,3,4,5,6]. These include atherosclerosis, hypertension, cataracts and Alzheimer’s disease [2,3,4,5,6], as well as syphilis, tuberculosis and viral-induced acute hepatic failure [5]. Transgenic rabbits are available to examine human cardiovascular disease and lipoprotein metabolism [6], as well as immune responses induced by papillomavirus, human immunodeficiency virus and ocular infection with herpesvirus [5].…”

Section: Introductionmentioning

confidence: 99%

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A Review on Mammary Tumors in Rabbits: Translation of Pathology into Medical Care

Schöniger¹,

Degner

Jasani³

et al. 2019

Animals

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Simple SummaryIn recent years mammary cancer has been increasingly recognized in pet rabbits. In addition to uterine carcinomas—the most common tumor of female rabbits—mammary cancer can also markedly reduce the life expectancy of pet rabbits. The aim of this review is to raise awareness for these tumors and to report recent progress in related research. Their detailed characterization will likely improve medical care for affected rabbits. Moreover, study results will contribute to comparative pathology and may reveal if the rabbit is a suitable model for certain types of breast cancer in humans. Available information suggests that most invasive cancer cases develop through stepwise progression from non-invasive forms. Thus, early recognition will likely improve a complete cancer cure. So far, the only treatment option is surgical excision and prognostic factors are unknown. Recent investigations have identified tumor features with likely prognostic value. They have also revealed differences and similarities to mammary tumors in other species and breast cancer in women. Despite these initial data, continued research is necessary to gain more insights into the development of these tumors and their molecular features.AbstractThe aim of this review is to raise awareness for mammary tumors in rabbits and to report progress in related research. Currently, a standardized tumor classification for rabbits is not available, prognostic factors are unknown and the only treatment option is surgical excision. Studies showed that affected rabbits have a wide age range and are nearly exclusively female or female spayed. Most mammary tumors are carcinomas. These may occur together with non-neoplastic or benign mammary lesions. Frequent microscopic findings are lipid droplets in tumor cells, secretory activity and microscopic heterogeneity. Since carcinomas are often negative for estrogen and progesterone receptors (ER-α/PR), modulation of receptor function will unlikely be beneficial for most rabbits. ER-α and PR status may have prognostic significance, since ER-α- or PR-negative tumors have significantly higher mitotic rates than ER-α- or PR-positive tumors. The frequent secretory activity of rabbit mammary tumors may suggest an influence of prolactin on tumorigenesis. Available data contribute to comparative pathology and are the basis for future molecular studies into the identification of additional prognostic factors and novel therapeutic options. They will also reveal the suitability of the rabbit as a model for certain types of breast cancer in women.

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Reactivity of selected markers of innate and adaptive immunity in rabbits experimentally infected with antigenic variants of RHD (Lagovirus europaeus/GI.1a)

2021

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Lagovirus europaeus/GI.1 causes a fatal viral condition in rabbits characterized by acute viral hepatitis and disseminated intravascular coagulation. Due to rapid viral and environmental changes variants (Lagovirus europaeus/GI.1a and GI.2) have appeared and few immunological studies were performed. The aim of the study was to determine innate and adaptive immunity parameters in rabbits infected with six Lagovirus europeus/GI.1a viruses. To achieve the goal several methods were used, i.e. cytometry, microscopy, biochemical and cytochemical tests, spectrophotometry. The results show that three immunotypes exists among the studied strains and they differ in innate (mainly) and adaptive immunity, partly depending on hemagglutination. The peak of changes is 24 h post infection in phagocytosis markers of polymorphonuclear cells and CD8+ T cells. Lagovirus europaeus/GI.1a strains differ from Lagovirus europaeus/GI.1 in terms of immunological response based on our previous work concerning the same parameters in immunological response against this disease.

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Author Correction: The wide utility of rabbits as models of human diseases

Abstract: This article was originally published under a CC BY-NC-SA License, but has now been made available under a CC BY 4.0 License.

Cited by 7 publications

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Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

A Review on Mammary Tumors in Rabbits: Translation of Pathology into Medical Care

Reactivity of selected markers of innate and adaptive immunity in rabbits experimentally infected with antigenic variants of RHD (Lagovirus europaeus/GI.1a)

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Author Correction: The wide utility of rabbits as models of human diseases

Abstract: This article was originally published under a CC BY-NC-SA License, but has now been made available under a CC BY 4.0 License.

Cited by 7 publications

References 0 publications

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8+TRMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8+TRMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

A Review on Mammary Tumors in Rabbits: Translation of Pathology into Medical Care

Reactivity of selected markers of innate and adaptive immunity in rabbits experimentally infected with antigenic variants of RHD (Lagovirus europaeus/GI.1a)

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Product

Resources

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Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8⁺T_RMCells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits