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This article is part of the supplement: AIDS Vaccine 2012

Open Access Oral presentation

Immune complexes can dampen inflammatory signaling at the mucosal surface during protective SIV vaccination

AJ Smith1*, SW Wietgrefe1, CS Reilly1, PJ Southern1, L Duan1, KE Perkey1, L Shang1, R Johnson2 and AT Haase1

  • * Corresponding author: AJ Smith

Author Affiliations

1 University of Minnesota , Minneapolis, MN, USA

2 New England Primate Research Center, Southborough, MA, USA

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Retrovirology 2012, 9(Suppl 2):O19  doi:10.1186/1742-4690-9-S2-O19

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/9/S2/O19


Published:13 September 2012

© 2012 Smith et al; licensee 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.

Background

The long-term goal for an efficacious HIV vaccine is to provide sterilizing protection from HIV infection. Thus far, this scenario has only been achieved experimentally using live-attenuated SIV vaccines. As such, great interest lies in identifying correlates of protection from a successful host response to pathogenic SIV. To this end, we have used a global genomics approach, tissue analysis, and explant cultures to identify immune complex (IC) signaling as an important component of a protective host response in the female reproductive tract (FRT) of animals vaccinated with the live-attenuated virus known as SIV mac239 ΔNef.

Methods

RNA from cervical tissue was purified for microarray analysis. Significant genes were functionally classified and protein expression determined using single-cell analytical procedures for tissue sections. FRT tissue was removed from healthy, uninfected, adult Rhesus macaques and cervix isolated/dissected into small tissue pieces for ex vivo culturing. WT SIVmac251 32H alone or SIV-specific ICs were added drop-wise to mucosal surfaces of explants and incubated for 24 hr at 37oC / 5% CO2.

Results

A genome-wide transcriptomics analysis revealed selective enrichment of an anti-inflammatory program upon virus exposure in SIVmac239-ΔNef-vaccinated animals, with localized expression of these anti-inflammatory mediators in the mucosal epithelium of the FRT, coinciding with dampened inflammation, limited CD4+ T cell infiltration, and stunted virus replication. Explant cultures derived from the FRT of Rhesus macaques were used as a physiological platform to identify the inhibitory Fc receptor for IgG, FcγRIIB, and carbohydrates in the Fc portion of SIV-specific ICs as centrally important in mediating this anti-inflammatory signaling program in mucosal epithelial cells.

Conclusion

These results highlight an unappreciated, non-neutralizing role for antiviral antibodies at mucosal surfaces and implicates the mucosal epithelial cell as an important host sensor that integrates external signals to elicit a host program that either promotes (inflammatory) or suppresses (anti-inflammatory) immunodeficiency virus infection.