IFN-α/β Signaling Is Required for CDG-Mediated CTL Generation and B Lymphocyte Activation

Ahmed E I Hamouda; Kai Schulze; Thomas Ebensen; Carlos Alberto Guzmán; Darío Lirussi

doi:10.3390/pharmaceutics14122821

IFN-α/β Signaling Is Required for CDG-Mediated CTL Generation and B Lymphocyte Activation

Pharmaceutics. 2022 Dec 16;14(12):2821. doi: 10.3390/pharmaceutics14122821.

Authors

Ahmed E I Hamouda^{1

2}, Kai Schulze¹, Thomas Ebensen¹, Carlos Alberto Guzmán¹, Darío Lirussi^{1

3}

Affiliations

¹ Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
² Currently at Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, 1050 Brussels, Belgium.
³ Instituto Nacional de Medicina Tropical (INMeT), Administración Nacional de Laboratorios e Institutos de Salud "Dr Carlos Malbrán", Puerto Iguazú 3370, Misiones, Argentina.

Abstract

Among cyclic di-nucleotides (CDN), both cyclic di-AMP (CDA) and di-GMP (CDG) are promising adjuvants and immune modulators. These molecules are not only able to induce profuse antibody production but also predominant T helper 1 and cytotoxic CD8 T lymphocytes (CTL) responses, which enable their use for vaccination against intracellular pathogens as well as in cancer immunotherapy. However, for their successful translation into the clinic, a comprehensive understanding of CDN mode of action is still essential. Consistent with evidence in the literature, we show here that IFN-α/β (Type I IFN) is crucial for CDG-mediated B cell activation. We recently determined the key role of type I IFN signaling for CDA-mediated enhancement of immunogenicity. Based on the biological activities of type I IFN, in this study, we hypothesized that it might also be required for CTL induction by CDG. We disclose here the mode of action of type I IFN signaling in CDG-mediated cross-presentation and subsequent CTL generation.

Keywords: IFN-α/β; adjuvant; cyclic di-nucleotides; immunomodulatory; vaccines.

Grants and funding

The present work was supported by grants from the European Community’s SeventhFramework Program, grant agreement # 601738 (UniVax, in part), Horizon 2020 grant reference # 730964 (TRANSVAC2, in part), and the Helmholtz Association (HAI-IDR in part). The funding agencies or they employees had no role in the design of search, neither in the related procedures (collection of data, software used, analyses of evidence or the interpretation of result). Funding organizations had no role or influence in the writing and publication of research results.