Interleukin-6 is essential for zwitterionic polysaccharide-mediated abscess formation.
Abscess formation associated with secondary peritonitis causes severe morbidity and can be fatal. Formation of abscesses requires the presence of CD4+ T-cells. Zwitterionic polysaccharides (ZPSs) represent a novel class of immunomodulatory bacterial antigens that stimulate CD4+ T-cells in a major histocompatibility complex (MHC) class II-dependent manner. The capsular polysaccharide Sp1 of Streptococcus pneumoniae serotype 1 possesses a zwitterionic charge with free amino groups and promotes T-cell-dependent abscess formation in an experimental mouse model. So far, nothing is known about the function of Interleukin (IL)-6 in intraperitoneal abscess formation. Here, we demonstrate that macrophages and dendritic cells (DCs), the most prevalent professional antigen-presenting cells involved in the formation of abscesses, secrete Interleukin (IL)-6 and are incorporated in the abscess capsule. Sp1 inhibits apoptosis of CD4+ T-cells and causes IL-17 expression by CD4+ T-cells in an IL-6-dependent manner. Abrogation of the Sp1-induced pleiotropic effects of IL-6 in IL-6-deficient mice and mice treated with an IL-6-specific neutralizing antibody results in significant inhibition of abscess formation. The data delineate the essential role of IL-6 in the linkage of innate and adaptive immunity in polysaccharide-mediated abscess formation.
Meemboor
Sonja
S
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne Medical Centre, Cologne, Germany.
Mertens
Janina
J
Flenner
Eva
E
Groneck
Laura
L
Zingarelli
Alessandra
A
Gamstätter
Thomas
T
Bessler
Martina
M
Seeger
Jens M
JM
Kashkar
Hamid
H
Odenthal
Margarete
M
Kalka-Moll
Wiltrud Maria
WM
D000038:Abscess / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016667:Bacterial Capsules / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010529:Peritoneal Cavity / Q000473:pathology; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D011135:Polysaccharides, Bacterial