Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma.
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.
Vermi
William
W
Department of Pathology and the Section of General Pathology and Immunology, University of Brescia, Italy.
Facchetti
Fabio
F
Riboldi
Elena
E
Heine
Holger
H
Scutera
Sara
S
Stornello
Sarah
S
Ravarino
Daniela
D
Cappello
Paola
P
Giovarelli
Mirella
M
Badolato
Raffaele
R
Zucca
Mario
M
Gentili
Francesca
F
Chilosi
Marco
M
Doglioni
Claudio
C
Ponzi
Alessandro Negro
AN
Sozzani
Silvano
S
Musso
Tiziana
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018416:Bartonella henselae / Q000302:isolation & purification; D002372:Cat-Scratch Disease / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D002415:Cats; D049109:Cell Proliferation; D002478:Cells, Cultured; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology*; D020825:T-Box Domain Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D051193:Toll-Like Receptors; D014157:Transcription Factors; D016753:Interleukin-10