Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma

William Vermi, Fabio Facchetti, Elena Riboldi, Holger Heine, Sara Scutera, Sarah Stornello, Daniela Ravarino, Paola Cappello, Mirella Giovarelli, Raffaele Badolato, Mario Zucca, Francesca Gentili, Marco Chilosi, Claudio Doglioni, Alessandro Negro Ponzi, Silvano Sozzani, Tiziana Musso

Research output: Contribution to journalArticle

Abstract

Dendritic cells (DCs) initiate adaptive immunity and regulate the inflammatory response by producing inflammatory chemokines. This study was aimed to elucidate their role in the pathogenesis of the suppurative granuloma induced by Bartonella henselae infection, which characterizes cat scratch disease (CSD). In vitro DC infection by B. henselae results in internalization of bacteria, phenotypic maturation with increased expression of HLA-DR and CD86, and induction of CD83, CD208, and CCR7. In comparison to LPS-activated DCs, B henselae-infected DCs produce higher amounts of IL-10, whereas the production of IL-12p70 is reduced. Infected DCs also produce high levels of CXCL8 and CXCL13, 2 chemokines active respectively on neutrophils and B lymphocytes. These results provide the molecular basis for the morphogenesis of CSD granuloma, which typically contains high numbers of neutrophils and B cells. Remarkably, CSD granulomas in vivo contain CXCL13-producing DCs. We further demonstrate that the B cells in CSD granulomas are represented by monocytoid B cells and, worth noting, they express T-bet, a transcription factor able to induce a T-independent immunoglobulin (Ig) class switch in B lymphocytes. These findings suggest that the humoral immune response to B henselae initiates in the extrafollicular areas of infected lymph nodes and is regulated by DCs.

Original languageEnglish
Pages (from-to)454-462
Number of pages9
JournalBlood
Volume107
Issue number2
DOIs
Publication statusPublished - Jan 15 2006

ASJC Scopus subject areas

  • Hematology

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    Vermi, W., Facchetti, F., Riboldi, E., Heine, H., Scutera, S., Stornello, S., Ravarino, D., Cappello, P., Giovarelli, M., Badolato, R., Zucca, M., Gentili, F., Chilosi, M., Doglioni, C., Ponzi, A. N., Sozzani, S., & Musso, T. (2006). Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma. Blood, 107(2), 454-462. https://doi.org/10.1182/blood-2005-04-1342