Volume 9 Supplement 2
Role of novel type I interferon epsilon in mucosal immunity
© Xi et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
Newly discovered type I interferon-epsilon (IFN-ε) is found to be constitutively expressed in mucosal tissues, i.e lung, reproductive tissue and intestine. Our previous studies have postulated that IFN-ε could play a role in modulating mucosal immunity. As HIV is a disease of the mucosae, we further evaluated the immuno-biology of IFN-ε in the mucosae and tested whether IFN-ε could be used as a mucosal adjuvant to enhance HIV-specific immunity.
Poxvirus (Vaccinia Virus and Fowl poxvirus) co-expressing HIV-1 gag/pol and interferon epsion (VV-HIV-IFN-ε or FPV-HIV-IFN-ε) were used in this study to evaluate immuno-biology and adjuvant activity of IFN-ε.
Firstly, VV-HIV-IFN-ε was utilized to study the immuno-biology of IFN-ε compared to IFN-α4 or IFN-β. Following intranasal (i.n.) VV-HIV-IFN-ε infection, a rapid VV clearance in lung was induced that correlated with 1) an elevated lung VV-specific CD8+CD107a+IFN-γ+, 2) up-regulated activation markers CD69/CD103 on CD8 T cells, 3) enhanced lymphocyte recruitment to lung alveoli with reduced inflammation and 4) heightened functional/cytotoxic CD8+CD4+ T cell subset (CD3hiCCR7hiCD62Llo) in lung lymph nodes. These responses were different to that observed following i.n. VV-HA-IFN-α4 or VV-HA-IFN-β infections. Secondly, intranasal/intramuscular (i.n./i.m.) heterologous prime-boost immunization (FPV-HIV-IFN-ε/VV-HIV-IFN-ε) was used to evaluated adjuvant activity of IFN-ε. Data indicated that IFN-ε induced elevated HIV-specific effector but not memory CD8 T cells responses in spleen, genito-rectal nodes and Peyer’s patch compared to the control (i.n. FPV-HIV/i.m. VV-HIV). Interestingly, unlike IFN-β and IFN-α4, IFN-ε uniquely induce elevated frequency of α4β7 and CCR9 expressing HIV-specific CD8 T cells in gut mucosae.
In conclusion, our data indicated that 1) IFN-ε can induced excellent T cell response in the mucosae especially lung and gut, and 2) rather than an vaccine adjuvant IFN-ε has the potential to be used as an anti-microbicide to prevent or reduced mucosal infection such as TB or HIV.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.