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

Intranasal infection with vaccinia virus co-expressing interferon epsilon (VV-HIV-IFN-epsilon) was used to evaluate the role of IFN-epsilon in mucosal immunity. VV-HIV-IFN-epsilon infection induced a rapid VV clearance in lung that correlated with (i) an elevated lung VV-specific CD8(+)CD107(a+)IFN-gamma(+) population expressing activation markers CD69/CD103, (ii) enhanced lymphocyte recruitment to lung alveoli with reduced inflammation, and (iii) an heightened functional/cytotoxic CD8(+)CD(4+) 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-alpha(4) or VV-HA-IFN-beta infections. When IFN-epsilon 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 alpha 4 beta 7 and CCR9 analysis indicated that unlike other type I IFNs, IFN-epsilon could promote migration of antigen-specific CD8+ T cells to the gut. Our results indicate that IFN-beta 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.