Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17.
Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23-mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii-induced immunopathology. Moreover, IL-23-dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down-regulated and dispensable. CD4(+) T cells were the main source of IL-22 in the small intestinal lamina propria. Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation.
Muñoz
Melba
M
Institute of Microbiology and Hygiene, Campus Benjamin Franklin, Charité Medical School, 12203 Berlin, Germany.
Heimesaat
Markus M
MM
Danker
Kerstin
K
Struck
Daniela
D
Lohmann
Uwe
U
Plickert
Rita
R
Bereswill
Stefan
S
Fischer
André
A
Dunay
Ildikò Rita
IR
Wolk
Kerstin
K
Loddenkemper
Christoph
C
Krell
Hans-Willi
HW
Libert
Claude
C
Lund
Leif R
LR
Frey
Oliver
O
Hölscher
Christoph
C
Iwakura
Yoichiro
Y
Ghilardi
Nico
N
Ouyang
Wenjun
W
Kamradt
Thomas
T
Sabat
Robert
R
Liesenfeld
Oliver
O
D000818:Animals; D005260:Female; D020381:Interleukin-17 / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology*; D007378:Interleukins / Q000502:physiology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014122:Toxoplasma / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology; D000097043:Interleukin-22
D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010879:Piperazines; D011743:Pyrimidines; D000097043:Interleukin-22; C453902:Ro 28-2653