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      The Regulatory Microenvironment in Feathers of Chickens Infected with Very Virulent Marek’s Disease Virus

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      Viruses
      MDPI AG

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          Abstract

          Vaccines against Marek’s disease can protect chickens against clinical disease; however, infected chickens continue to propagate the Marek’s disease virus (MDV) in feather follicles and can shed the virus into the environment. Therefore, the present study investigated if MDV could induce an immunoregulatory microenvironment in feathers of chickens and whether vaccines can overcome the immune evasive mechanisms of MDV. The results showed an abundance of CD4+CD25+ and CD4+ transforming growth factor-beta (TGF-β)+ T regulatory cells in the feathers of MDV-infected chickens at 21 days post-infection. In contrast, vaccinated chickens had a lower number of regulatory T cells. Furthermore, the expression of TGF-β and programmed cell death receptor (PD)-1 increased considerably in the feathers of Marek’s disease virus-infected chickens. The results of the present study raise the possibility of an immunoregulatory environment in the feather pulp of MDV-infected chickens, which may in turn favor replication of infectious MDV in this tissue. Exploring the evasive strategies employed by MDV will facilitate the development of control measures to prevent viral replication and transmission.

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          Perforin and granzymes: function, dysfunction and human pathology.

          A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.
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            The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection.

            The programmed cell death 1 (PD-1) surface receptor binds to two ligands, PD-L1 and PD-L2. Studies have shown that PD-1-PD-L interactions control the induction and maintenance of peripheral T cell tolerance and indicate a previously unknown function for PD-L1 on nonhematopoietic cells in protecting tissues from autoimmune attack. PD-1 and its ligands have also been exploited by a variety of microorganisms to attenuate antimicrobial immunity and facilitate chronic infection. Here we examine the functions of PD-1 and its ligands in regulating antimicrobial and self-reactive T cell responses and discuss the therapeutic potential of manipulating this pathway.
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              Mechanisms of foxp3+ T regulatory cell-mediated suppression.

              Foxp3(+) T regulatory (Treg) cells control all aspects of the immune response. Here, I will review the in vitro model systems that have been developed to define the mechanisms used by Treg cells to suppress a large number of distinct target cell types. These mechanisms can be broadly divided into those that target T cells (suppressor cytokines, IL-2 consumption, cytolysis) and those that primarily target antigen-presenting cells (decreased costimulation or decreased antigen presentation). Although multiple mechanisms for Treg cell suppression have been shown in vitro, it is unclear whether the same or different mechanisms are used by Treg cells in vivo. An increase in our understanding of Treg cell suppressor mechanisms will offer an insight into how Treg cell function can be manipulated either positively or negatively in vivo.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                VIRUBR
                Viruses
                Viruses
                MDPI AG
                1999-4915
                January 2022
                January 09 2022
                : 14
                : 1
                : 112
                Article
                10.3390/v14010112
                35062316
                8ffe8615-d10a-427e-9d33-c350abe03c5b
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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