Publications & Reports

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

Xi Y, Day SL, Jackson RJ, Ranasinghe C
Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.

Abstract

Intranasal infection with vaccinia virus co-expressing interferon epsilon (VV-HIV-IFN-varepsilon) was used to evaluate the role of IFN-varepsilon in mucosal immunity. VV-HIV- IFN-varepsilon infection induced a rapid VV clearance in lung that correlated with (i) an elevated lung VV-specific CD8(+)CD107a(+)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(+)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-alpha(4) or VV-HA-IFN-beta infections. When IFN-varepsilon 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 alpha4beta7 and CCR9 analysis indicated that unlike other type I IFNs, IFN-varepsilon could promote migration of antigen-specific CD8(+)T cells to the gut. Our results indicate that IFN-varepsilon 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.

Publication

  • Journal: Mucosal Immunology
  • Published: 01/11/2012
  • Volume: 5
  • Issue: 6
  • Pagination: 610-622

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