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Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D.
Al-Ahdal, Mohammed N; Murugaiah, Valarmathy; Varghese, Praveen M; Abozaid, Suhair M; Saba, Iram; Al-Qahtani, Ahmed Ali; Pathan, Ansar A; Kouser, Lubna; Nal, Béatrice; Kishore, Uday.
Afiliação
  • Al-Ahdal MN; Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • Murugaiah V; Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
  • Varghese PM; Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
  • Abozaid SM; Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • Saba I; Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • Al-Qahtani AA; Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
  • Pathan AA; Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
  • Kouser L; Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
  • Nal B; Allergy & Clinical Immunology Inflammation, Repair and Development, Imperial College London, London, United Kingdom.
  • Kishore U; Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
Front Immunol ; 9: 1586, 2018.
Article em En | MEDLINE | ID: mdl-30105014
Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV). SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV. Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment. In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-ß, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line. rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding. Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity. Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines. In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF. These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner. Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Infecções por Orthomyxoviridae / Proteína D Associada a Surfactante Pulmonar Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Infecções por Orthomyxoviridae / Proteína D Associada a Surfactante Pulmonar Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article