title: Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus.
abstract: Highly pathogenic avian influenza virus (H5N1) is an emerging pathogen with the potential to cause great harm to humans, and there is concern about the potential for a new influenza pandemic. This virus is resistant to the antiviral effects of interferons and tumor necrosis factor-alpha. However, the mechanism of interferon-independent protective innate immunity is not well understood. The prophylactic effects of chitin microparticles as a stimulator of innate mucosal immunity against a recently obtained strain of H5N1 influenza virus infection were examined in mice. Clinical parameters and the survival rate of mice treated by intranasal application of chitin microparticles were significantly improved compared to non-treated mice after a lethal influenza virus challenge. Flow cytometric analysis revealed that the number of natural killer cells that expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and that had migrated into the cervical lymph node was markedly increased (26-fold) after intranasal treatment with chitin microparticles. In addition, the level of IL-6 and interferon-gamma-inducible protein-10 (IP-10) in the nasal mucosa after H5N1 influenza virus challenge was decreased by prophylactic treatment with chitin microparticles. These results suggest that prophylactic intranasal administration of chitin microparticles enhanced the local accumulation of natural killer cells and suppressed hyper-induction of cytokines, resulting in an innate immune response to prevent pathogenesis of H5N1 influenza virus.
authors: Department of Pathology, National Institute of Infectious Diseases, Gakuen, Musashimurayama-shi, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Ichinohe
authors: Noriyo
authors: N
authors: Nagata
authors: Peter
authors: P
authors: Strong
authors: Shin-ichi
authors: S
authors: Tamura
authors: Hidehiro
authors: H
authors: Takahashi
authors: Ai
authors: A
authors: Ninomiya
authors: Masaki
authors: M
authors: Imai
authors: Takato
authors: T
authors: Odagiri
authors: Masato
authors: M
authors: Tashiro
authors: Hirofumi
authors: H
authors: Sawa
authors: Joe
authors: J
authors: Chiba
authors: Takeshi
authors: T
authors: Kurata
authors: Tetsutaro
authors: T
authors: Sata
authors: Hideki
authors: H
authors: Hasegawa
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000032:analysis / Q000276:immunology; D002686:Chitin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000737:chemistry / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis
chemical_list: D000998:Antiviral Agents; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D015850:Interleukin-6; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D002686:Chitin