Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling

Abstract

Subunit vaccines drive immune cell-cell interactions in the lymph node (LN), yet it remains unclear how distinct adjuvants influence the chemokines responsible for this interaction in the tissue. Here, we tested the hypothesis that classic Th1-polarizing vaccines elicit a unique chemokine signature in the LN compared to other adjuvants. Polyinosinic:polycytidylic acid (Poly I:C) vaccination resulted in dynamic upregulation of CXCL9 that was localized in the interfollicular region, a response not observed after vaccination with alum or a combination of alum and poly I:C. Experiments using in vivo mouse models and live ex vivo LN slices revealed that poly I:C vaccination resulted in a type-I IFN response in the LN that led to the secretion of IFNγ, and type-I IFN and IFNγ were required for CXCL9 expression in this context. CXCL9 expression in the LN was correlated with an IgG2c antibody polarization after vaccination; however, genetic depletion of the receptor for CXCL9 did not prevent the development of this polarization. Additionally, we measured secretion of CXCL9 from ex vivo LN slices after stimulation with a variety of adjuvants and confirmed that adjuvants that induced IFNγ responses also promoted CXCL9 expression. Taken together, these results identify a CXCL9 signature in a suite of Th1-polarizing adjuvants and determined the pathway involved in driving CXCL9 in the LN, opening avenues to target this chemokine pathway in future vaccines.

Keywords: Antibody; Extrafollicular; Interferon gamma-induced protein 10 (IP-10); Monokine induced by gamma interferon (MIG); Polarization; Tissue slices.