title: Intranasal administration of the TLR2 agonist Pam2Cys provides rapid protection against influenza in mice.
abstract: The protective role played by the innate immune system during early stages of infection suggests that compounds which stimulate innate responses could be used as antimicrobial or antiviral agents. In this study, we demonstrate that the Toll-like receptor-2 agonist Pam2Cys, when administered intranasally, triggers a cascade of inflammatory and innate immune signals, acting as an immunostimulant by attracting neutrophils and macrophages and inducing secretion of IL-2, IL-6, IL-10, IFN-γ, MCP-1 and TNF-α. These changes provide increased resistance against influenza A virus challenge and also reduce the potential for transmission of infection. Pam2Cys treatment also reduced weight loss and lethality associated with virulent influenza virus infection in a Toll-like receptor-2-dependent manner. Treatment did not affect the animals' ability to generate an adaptive immune response, measured by the induction of functional influenza A virus-specific CD8(+) T cells following exposure to virus. Because this compound demonstrates efficacy against distinct strains of influenza, it could be a candidate for development as an agent against influenza and possibly other respiratory pathogens.
authors: Department of Microbiology & Immunology, The University of Melbourne, Parkville 3010, Victoria, Australia.
authors: Amabel C L
authors: AC
authors: Tan
authors: Edin J
authors: EJ
authors: Mifsud
authors: Weiguang
authors: W
authors: Zeng
authors: Kathryn
authors: K
authors: Edenborough
authors: Jodie
authors: J
authors: McVernon
authors: Lorena E
authors: LE
authors: Brown
authors: David C
authors: DC
authors: Jackson
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D009980:Influenza A virus / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D055666:Lipopeptides / Q000008:administration & dosage* / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000998:Antiviral Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007378:Interleukins; D055666:Lipopeptides; C552442:S-(2,3-bis(palmitoyloxy)propyl)cysteine; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma