PMID- 16189275 OWN - NLM STAT- MEDLINE DCOM- 20060207 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 107 IP - 2 DP - 2006 Jan 15 TI - Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma. PG - 454-62 AB - 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. FAU - Vermi, William AU - Vermi W AD - Department of Pathology and the Section of General Pathology and Immunology, University of Brescia, Italy. FAU - Facchetti, Fabio AU - Facchetti F FAU - Riboldi, Elena AU - Riboldi E FAU - Heine, Holger AU - Heine H FAU - Scutera, Sara AU - Scutera S FAU - Stornello, Sarah AU - Stornello S FAU - Ravarino, Daniela AU - Ravarino D FAU - Cappello, Paola AU - Cappello P FAU - Giovarelli, Mirella AU - Giovarelli M FAU - Badolato, Raffaele AU - Badolato R FAU - Zucca, Mario AU - Zucca M FAU - Gentili, Francesca AU - Gentili F FAU - Chilosi, Marco AU - Chilosi M FAU - Doglioni, Claudio AU - Doglioni C FAU - Ponzi, Alessandro Negro AU - Ponzi AN FAU - Sozzani, Silvano AU - Sozzani S FAU - Musso, Tiziana AU - Musso T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050927 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CXCL13 protein, human) RN - 0 (Chemokine CXCL13) RN - 0 (Chemokines, CXC) RN - 0 (Immunoglobulin G) RN - 0 (Lipopolysaccharides) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 0 (Toll-Like Receptors) RN - 0 (Transcription Factors) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - B-Lymphocytes/immunology/metabolism MH - Bartonella henselae/isolation & purification MH - Cat-Scratch Disease/immunology/microbiology/*pathology MH - Cats MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CXCL13 MH - Chemokines, CXC/*metabolism MH - Dendritic Cells/*metabolism MH - Granuloma/immunology/microbiology/*pathology MH - Humans MH - Immunoglobulin G/metabolism MH - Interleukin-10/metabolism MH - Lipopolysaccharides/pharmacology MH - Lymph Nodes/*pathology MH - T-Box Domain Proteins MH - T-Lymphocytes/immunology/metabolism MH - Toll-Like Receptors/immunology/metabolism MH - Transcription Factors/metabolism EDAT- 2005/09/29 09:00 MHDA- 2006/02/08 09:00 CRDT- 2005/09/29 09:00 PHST- 2005/09/29 09:00 [pubmed] PHST- 2006/02/08 09:00 [medline] PHST- 2005/09/29 09:00 [entrez] AID - S0006-4971(20)67277-9 [pii] AID - 10.1182/blood-2005-04-1342 [doi] PST - ppublish SO - Blood. 2006 Jan 15;107(2):454-62. doi: 10.1182/blood-2005-04-1342. Epub 2005 Sep 27.