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-) was used to evaluate the role of IFN-in mucosal immunity. VV-HIV-IFN-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-∈ 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-could promote migration of antigen-specific CD8+ T cells to the gut. Our results indicate that IFN-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. Show more