Murine ileitis after intracellular parasite infection is controlled by TGF-beta-producing intraepithelial lymphocytes.
OBJECTIVE
Acute inflammatory ileitis occurs in susceptible (C57BL/6) mice after oral infection with Toxoplasma gondii. Overproduction of interferon (IFN)-gamma and synthesis of nitric oxide mediate the inflammation. We evaluated the role of transforming growth factor (TGF)-beta produced by intraepithelial lymphocytes (IELs) in this process.


METHODS
We analyzed the histologic and immunologic consequences of adoptive transfer of antigen-primed IELs into susceptible mice treated with anti-TGF-beta before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-beta.


RESULTS
Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-beta. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-beta. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-gamma production. In vitro, primed IELs reduce the production of inflammatory chemokines by infected enterocytes and IFN-gamma by splenocytes.


CONCLUSIONS
Regulation of the ileal inflammatory process resulting from T. gondii is dependent on TGF-beta-producing IELs. The IELs are an essential component in gut homeostasis after oral infection with this parasite.
Laboratoire Associe Institut National de la Recherche Agronomique d'Immunologie Parasitaire, Faculte de Pharmacie, Tours, France.
D
D
Buzoni-Gatel
H
H
Debbabi
F J
FJ
Mennechet
V
V
Martin
A C
AC
Lepage
J D
JD
Schwartzman
L H
LH
Kasper
D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004198:Disease Susceptibility; D015536:Down-Regulation; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D007079:Ileitis / Q000469:parasitology* / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D014122:Toxoplasma; D014123:Toxoplasmosis; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D018925:Chemokines; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta