Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling.
Besides Peyer's patches, solitary intestinal lymphoid tissue (SILT) provides a structural platform to efficiently initiate immune responses in the murine small intestine. SILT consists of dynamic lymphoid aggregates that are heterogeneous in size and composition, ranging from small clusters of mostly lineage-negative cells known as cryptopatches to larger isolated lymphoid follicles rich in B cells. In this study, we report that in chemokine receptor CCR7-deficient mice SILT is enlarged, although unchanged in frequency and cellular composition compared with wild-type mice. This phenotype is conferred by bone marrow-derived cells and is independent of the presence of intestinal bacteria. Remarkably, particularly small-sized SILT predominates in germfree wild-type mice. Colonization of wild-type mice with commensal bacteria provokes an adjustment of the spectrum of SILT to that observed under specific pathogen-free conditions by the conversion of pre-existing lymphoid structures into larger-sized SILT. In conclusion, our findings establish that intestinal microbes influence the manifestation of gut-associated lymphoid tissues and identify CCR7 signaling as an endogeneous factor that controls this process.
Pabst
Oliver
O
Institute of Immunology, Hannover Medical School, Hannover, Germany. Pabst.Oliver@mh-hannover.de
Herbrand
Heike
H
Friedrichsen
Michaela
M
Velaga
Sarvari
S
Dorsch
Martina
M
Berhardt
Günter
G
Worbs
Tim
T
Macpherson
Andrew J
AJ
Förster
Reinhold
R
D000222:Adaptation, Physiological / Q000276:immunology*; D000818:Animals; D001419:Bacteria / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D006965:Hyperplasia; D016130:Immunophenotyping; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine