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      Tick–Virus–Host Interactions at the Cutaneous Interface: The Nidus of Flavivirus Transmission

      review-article
      1 , 1 , 2 , 3 , *
      Viruses
      MDPI
      tick, flavivirus, saliva, skin, cutaneous, interface, feeding

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          Abstract

          Tick-borne viral diseases continue to emerge in the United States, as clearly evident from the increase in Powassan encephalitis virus, Heartland virus, and Bourbon virus infections. Tick-borne flaviviruses (TBFVs) are transmitted to the mammalian host along with the infected tick saliva during blood-feeding. Successful tick feeding is facilitated by a complex repertoire of pharmacologically active salivary proteins/factors in tick saliva. These salivary factors create an immunologically privileged micro-environment in the host’s skin that influences virus transmission and pathogenesis. In this review, we will highlight tick determinants of TBFV transmission with a special emphasis on tick–virus–host interactions at the cutaneous interface.

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          Most cited references37

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          Skin immune sentinels in health and disease.

          Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.
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            Mechanisms regulating skin immunity and inflammation.

            Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.
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              An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks.

              Over 8000 expressed sequence tags from six different salivary gland cDNA libraries from the tick Ixodes scapularis were analyzed. These libraries derive from feeding nymphs infected or not with the Lyme disease agent, Borrelia burgdorferi, from unfed adults, and from adults feeding on a rabbit for 6-12 h, 18-24 h, and 3-4 days. Comparisons of the several libraries led to identification of several significantly differentially expressed transcripts. Additionally, over 500 new predicted protein sequences are described, including several novel gene families unique to ticks; no function can be presently ascribed to most of these novel families. Among the housekeeping-associated transcripts, we highlight those enzymes associated with post translation modification of amino acids, particularly those forming sulfotyrosine, hydroxyproline, and carboxyl-glutamic acid. Results support the hypothesis that gene duplication, most possibly including genome duplications, is a major player in tick evolution.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                07 July 2018
                July 2018
                : 10
                : 7
                : 362
                Affiliations
                [1 ]Department of Pathology, University of Texas Medical Branch (UTMB), 301 University Boulevard, Galveston, TX 77555-0609, USA
                [2 ]Institute for Human Infections and Immunity, University of Texas Medical Branch (UTMB), Galveston, TX 77555-0609, USA
                [3 ]Center for Tropical Diseases, University of Texas Medical Branch (UTMB), Galveston, TX 77555-0609, USA
                Author notes
                [* ]Correspondence: sathanga@ 123456utmb.edu ; Tel.: +1-409-747-2412
                Author information
                https://orcid.org/0000-0003-0494-9670
                Article
                viruses-10-00362
                10.3390/v10070362
                6071252
                29986483
                cd3051f7-b3cd-478f-9132-0cc42c456fe8
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 June 2018
                : 06 July 2018
                Categories
                Review

                Microbiology & Virology
                tick,flavivirus,saliva,skin,cutaneous,interface,feeding
                Microbiology & Virology
                tick, flavivirus, saliva, skin, cutaneous, interface, feeding

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