Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization.
BACKGROUND
IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis.


RESULTS
We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro.


CONCLUSIONS
From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/-)-mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC.
Müller
Martina
M
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
Fink
Kerstin
K
Geisel
Julia
J
Kahl
Frauke
F
Jilge
Burghardt
B
Reimann
Jörg
J
Mach
Nicolas
N
Autenrieth
Ingo B
IB
Frick
Julia S
JS
D000818:Animals; D001407:Bacillus / Q000302:isolation & purification* / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha