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      Effects of Trichophyton mentagrophytes infection on the immune response of rabbits

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          Abstract

          Background

          Rabbit breeding has developed into a large-scale industry, and as such, the incidence of dermatophytosis in rabbits has become increasingly common. A rabbit model with Trichophyton mentagrophytes infection was established to study the changes within the immune responses after fungal infection.

          Methods

          After the T. mentagrophytes challenge on skin, pathogens on the skin were isolated from the rabbits in the fungal infection (FI) groups 20 days. Fungal observation under microscope were carried out. Identification of strains was achieved by polymerase chain reaction (PCR) using the CDR1 gene. The collected anticoagulant blood samples were analyzed for various blood cell parameters. The levels of antibodies, including IgM and IgA, cytokines, including IL-2, IL-6, and macrophage colony-stimulating factor (M-CSF), and soluble CD4 and CD8 in the serum of the FI group vs. the control group were determined independently. RNA isolation from blood samples and fluorescence-based quantitative PCR were carried out for the mRNA level of M-csf 20 days after fungal challenge.

          Results

          Our model resulted in typical symptoms of dermatophytosis on rabbit skin after challenged with fungus. Pathogens isolated from the infected rabbit skin were confirmed to be T. mentagrophytes by microscopic examination and PCR. The number of lymphocytes in the blood of the FI group was significantly decreased in comparison to the control group 2 days after the fungal challenge, but was significantly increased in comparison the control group 10 days after the fungal challenge ( P < 0.01). Platelet counts of the FI group were significantly higher than in the control group at 2 ( P < 0.05), 10 ( P < 0.05), and 20 ( P < 0.01) days after fungal challenge. The red blood cell distribution width of the FI group was significantly increased in comparison to that of the control group at 2, 10, and 20 days after fungal challenge ( P < 0.01 for all days). The levels of antibodies (immunoglobulin (Ig) M and IgA ( P < 0.01)), cytokines (interleukin (IL)-6 ( P < 0.01), macrophage colony-stimulating factor (M-CSF) ( P < 0.05)), and soluble CD4 ( P < 0.01) and CD8 ( P < 0.01) in the serum were significantly different between the FI and control groups. Serum M-csf mRNA level of the FI group was significantly higher than the control group 20 days after fungal challenge ( P < 0.01).

          Conclusions

          This study demonstrates how the immune system responds to infection with T. mentagrophytes and provides potential targets for the prevention and treatment of dermatophytosis.

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          Most cited references18

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          Can mean platelet volume and red blood cell distribution width show disease activity in rheumatoid arthritis?

          To evaluate the relationship between mean platelet volume (MPV) and red cell distribution width (RDW), and disease activity in rheumatoid arthritis (RA).
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            Autocrine Type I IFN Signaling in Dendritic Cells Stimulated with Fungal β-Glucans or Lipopolysaccharide Promotes CD8 T Cell Activation

            Type I interferons (IFNs) are key mediators of immune defense against viruses and bacteria. Type I IFNs have also been implicated in protection against fungal infection, but their roles in anti-fungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal β-glucans stimulate IFN-β production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of β-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal β-glucan particle-stimulated DCs. We demonstrate that β-glucan-stimulated DCs induce CD8 T cell proliferation, activation marker (CD44 and CD69) expression, and production of IFN-γ, IL-2 and granzyme B. Moreover, we show that type I IFNs support robust CD8 T cell activation (proliferation, and IFN-γ and granzyme B production) by β-glucan-stimulated DCs both in vitro and in vivo due to autocrine effects on the DCs. Specifically, type I IFNs promote antigen presentation on MHC I molecules, CD86 and CD40 expression, and the production of IL-12 p70, IL-2, IL-6 and TNF-α by β-glucan-stimulated DCs. We also demonstrate a role for autocrine type I IFN signaling in bacterial lipopolysaccharide (LPS)-induced DC maturation, although in the context of LPS stimulation, this mechanism is not so critical for CD8 T cell activation (promotes IFN-γ production, but not proliferation or granzyme B production). This study provides insight into the mechanisms underlying CD8 T cell activation during infection, which may be useful in the rational design of vaccines directed against pathogens and tumors.
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              Research of Mrr1, Cap1 and MDR1 in Candida albicans resistant to azole medications

              The aim of the present study was to investigate the association between Mrr1, adenylyl cyclase-associated protein 1 (Cap1) and multi-drug resistance gene 1 (MDR1), and to assess the mutations in Mrr1 and Cap1 in azole-resistant Candida albicans strains. The study isolated 68 C. albicans strains from patients with vulvovaginal candidiasis. Drug susceptibility testing was conducted to characterize the resistance profile of these strains to fluconazole, itraconazole and voriconazole. Polymerase chain reaction (PCR) amplification was performed for Cap1 and Mrr1, and the PCR products were sequenced to identify any mutations. Reverse transcription-quantitative PCR was performed to measure Cap1, Mrr1 and MDR1 mRNA in C. albicans strains. The results of the present study indicated S381N, P311S and A390T missense mutations in Cap1 and T917M, T923I, N937K, E1020Q, F1032L and S1037L missense mutations in Mrr1 in azole-resistant C. albicans strains. Fluconazole-resistant strains had significantly elevated Cap1 and MDR1 mRNA levels compared with fluconazole-sensitive strains (P<0.01). The mRNA levels of Cap1, Mrr1 and MDR1 were significantly increased in the strains resistant to all three of fluconazole, itraconazole and voriconazole compared with strains sensitive to the three agents (P<0.001, P=0.037 and P<0.001, respectively). Cap1 expression was positively correlated with MDR1 expression in fluconazole-resistant strains (P<0.05). No significant correlation was observed between Cap1, Mrr1 and MDR1 in the strains resistant to fluconazole, itraconazole or voriconazole. The results of the present study suggested that fluconazole resistance may involve MDR1 overexpression mediated by Cap1 overexpression. Cross-resistance between fluconazole, itraconazole and voriconazole may be associated with mutations in Cap1 and Mrr1, rather than their overexpression. In addition, the present study also revealed two novel mutations in Mrr1; T917M and T923I. These findings may provide a basis for elucidating the molecular mechanisms of and improving therapeutic treatments to tackle azole resistance.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                20 September 2019
                2019
                : 7
                : e7632
                Affiliations
                [1 ]Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences , Hangzhou, China
                [2 ]Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences , Hangzhou, Zhejiang Province, China
                Article
                7632
                10.7717/peerj.7632
                6756135
                4f743fd0-546b-46d9-8217-251c4e8bba89
                ©2019 Xiao et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 15 April 2019
                : 6 August 2019
                Funding
                Funded by: National Rabbit Industry Project of China
                Award ID: nycytx-44-3-2
                Funded by: National Natural Science Foundation
                Award ID: 31402241
                Funded by: Basic Public Welfare Research Projects in Zhejiang Province
                Award ID: LGN18C180003
                Funded by: Zhejiang Province
                Award ID: 2016C02054-10
                This animal challenge model experiment and the design of the study and collection in this study was funded by the National Rabbit Industry Project of China (nycytx-44-3-2) and the RT-PCR, ELISA experiment and analysis and interpretation of data and in writing the manuscript were funded by the National Natural Science Foundation (31402241) and Basic Public Welfare Research Projects in Zhejiang Province (LGN18C180003) and Key research and development plan of Zhejiang Province (No. 2016C02054-10). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Veterinary Medicine
                Dermatology
                Immunology

                trichophyton mentagrophytes,immune response indices,dermatophytosis,rabbits

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