title: Role of novel type I interferon epsilon in viral infection and mucosal immunity.
abstract: Intranasal infection with vaccinia virus co-expressing interferon epsilon (VV-HIV-IFN-ε) was used to evaluate the role of IFN-ε in mucosal immunity. VV-HIV- IFN-ε infection induced a rapid VV clearance in lung that correlated with (i) an elevated lung VV-specific CD8(+)CD107a(+)IFN-γ(+) population expressing activation markers CD69/CD103, (ii) enhanced lymphocyte recruitment to lung alveoli with reduced inflammation, and (iii) an heightened functional/cytotoxic CD8(+)CD4(+) T-cell subset (CD3(hi)CCR7(hi)CD62L(lo)) in lung lymph nodes. These responses were different to that observed with intranasal VV-HA-IFN-α(4) or VV-HA-IFN-β infections. When IFN-ε was used in an intranasal/intramuscular heterologous HIV prime-boost immunization, elevated HIV-specific effector, but not memory CD8(+)T cells responses, were observed in spleen, genito-rectal nodes, and Peyer's patch. Homing marker α4β7 and CCR9 analysis indicated that unlike other type I IFNs, IFN-ε could promote migration of antigen-specific CD8(+)T cells to the gut. Our results indicate that IFN-ε has a unique role in the mucosae and most likely can be used to control local lung and/or gut infections (i.e., microbicide) such as tuberculosis, HIV-1, or sexually transmitted diseases.
authors.affiliation: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xi
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Day
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: Charani
authors.initials: C
authors.lastname: Ranasinghe
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007114:Immunization; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007372:Interferons / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D014614:Vaccines, Synthetic; C578688:interferon-epsilon, mouse; D007372:Interferons