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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 183; p. 156731
• Main Authors: Ball, Alexander G., Morgaenko, Katerina, Anbaei, Parastoo, Ewald, Sarah E., Pompano, Rebecca R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2024
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibody; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Chemokine CXCL9 - metabolism; Extrafollicular; Female; Interferon gamma-induced protein 10 (IP-10); Interferon Type I - metabolism; Interferon-gamma - metabolism; Lymph Nodes - immunology; Lymph Nodes - metabolism; Mice; Mice, Inbred C57BL; Monokine induced by gamma interferon (MIG); Polarization; Poly I-C - pharmacology; Signal Transduction; Th1 Cells - immunology; Th1 Cells - metabolism; Tissue slices; Vaccination; IFN; Polarization; Interferon gamma-induced protein 10 (IP-10); LN; Monokine induced by gamma interferon (MIG); Antibody; Tissue slices; Extrafollicular
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2024.156731

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•CXCL9 was upregulated after vaccination with Th1 but not Th2 polarizing adjuvants.•Poly I:C induced IFNα + cells, IFNγ + cells, and CXCL9 in the interfollicular region.•IFNγ signaling was required and sufficient for upregulating CXCL9 in the lymph node.•IgG2c antibody polarization was correlated with CXCL9 expression.•CXCR3 was not required for IgG2c polarization after poly I:C vaccination.
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.