Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.
Enteropathogenic Yersinia enterocolitica (Ye) enters the host via contaminated food. After colonisation of the small intestine Ye invades the Peyer's patches (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs), spleen and liver. Whether Ye uses other invasion routes and which pathogenicity factors are required remains elusive. Oral infection of lymphotoxin-β-receptor deficient mice lacking PPs and MLNs with Ye revealed similar bacterial load in the spleen 1h post infection as wild-type mice, demonstrating a PP-independent dissemination route for Ye. Immunohistological analysis of the small intestine revealed Ye in close contact with mononuclear phagocytes (MPs), specifically CX3CR1(+) monocyte-derived cells (MCs) as well as CD103(+) dendritic cells (DCs). This finding was confirmed by flow cytometry and imaging flow cytometry analysis of lamina propria (LP) leukocytes showing CD103(+) DCs and MCs with intracellular Ye. Uptake of Ye by LP CD103(+) DCs and MCs was dependent on the pathogenicity factor invasin, whereas the adhesin YadA was dispensable as demonstrated by Ye deletion mutants. Furthermore, Ye were found exclusively associated with CD103(+) DCs in the MLNs from wild-type mice, but not from CCR7(-/-) mice, demonstrating a CCR7 dependent transport of Ye by CD103(+) DCs from LP to the MLNs. In contrast, dissemination of Ye to the spleen was dependent on MCs as significantly less Ye could be recovered from the spleen of CX3CR1(GFP/GFP) mice compared to wild-type mice. Altogether, MCs and CD103(+) DCs contribute to immediate invasion and dissemination of Ye. This together with data from other bacteria suggests MPs as general pathogenic entry site in the intestine.
Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany; Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany.
Doreen
D
Drechsler-Hake
Department of Internal Medicine II, University of Tübingen, 72076 Tübingen, Germany.
Hanin
H
Alamir
Department of Internal Medicine II, University of Tübingen, 72076 Tübingen, Germany.
Julia
J
Hahn
Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany; Department of Internal Medicine II, University of Tübingen, 72076 Tübingen, Germany.
Manina
M
Günter
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), Partner-site Tübingen, 72076 Tübingen, Germany.
Samuel
S
Wagner
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), Partner-site Tübingen, 72076 Tübingen, Germany.
Monika
M
Schütz
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany.
Erwin
E
Bohn
Department of Woman's Health, University of Tübingen, 72076 Tübingen, Germany.
Katja
K
Schenke-Layland
Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Fabio
F
Pisano
Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Petra
P
Dersch
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany; German Center for Infection Research (DZIF), Partner-site Tübingen, 72076 Tübingen, Germany.
Ingo B
IB
Autenrieth
Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany; Department of Internal Medicine II, University of Tübingen, 72076 Tübingen, Germany. Electronic address: stella.autenrieth@med.uni-tuebingen.de.
Stella E
SE
Autenrieth
D000818:Animals; D058491:Bacterial Load; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008099:Liver / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes / Q000382:microbiology*; D013154:Spleen / Q000382:microbiology; D013997:Time Factors; D015009:Yersinia Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D015008:Yersinia enterocolitica / Q000276:immunology* / Q000502:physiology*
Dendritic cell; Dissemination; Infection; Intestinal invasion; Mononuclear phagocytes; Yersinia