Role of novel type I interferon epsilon in viral infection and mucosal immunity

• Published in: Mucosal immunology Vol. 5; no. 6; pp. 610 - 622
• Main Authors: Xi, Yang, Day, Stephanie L, Jackson, Ronald J, Ranasinghe, Charani
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2012
• Subjects: Administration, Intranasal; AIDS Vaccines - administration & dosage; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Animals; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Female; Genetic Vectors - immunology; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - immunology; Immunity, Mucosal - drug effects; Immunization; Injections, Intramuscular; Injections, Intraperitoneal; Interferons - genetics; Interferons - immunology; Lung - drug effects; Lung - immunology; Lung - virology; Mice; Mice, Inbred BALB C; Peyer's Patches - drug effects; Peyer's Patches - immunology; Peyer's Patches - virology; Spleen - drug effects; Spleen - immunology; Spleen - virology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - virology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccinia - immunology; Vaccinia - prevention & control; Vaccinia - virology; Vaccinia virus - drug effects; Vaccinia virus - genetics; Vaccinia virus - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2012.35

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.