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 Blood, 15 January 2006, Vol. 107, No. 2, pp. 454-462.
Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-04-1342.

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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

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, and Tiziana Musso

From the Department of Pathology and the Section of General Pathology and Immunology, University of Brescia, Italy; Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany; Departments of Public Health and Microbiology, Medicine and Experimental Oncology, and Clinical and Biological Sciences, University of Turin, Italy; Center for Experimental Research and Medical Studies (CERMS), S. Giovanni Battista Hospital, Turin, Italy; Department of Pediatrics, University of Brescia, Spedali civili, Italy; Department of Pathology, University of Verona, Italy; Department of Pathology, San Raffaele Hospital, Milan, Italy; and Istituto Ricerche Farmacologiche "Mario Negri," Milan, Italy.

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.


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