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.
Buzoni-Gatel
D
D
Laboratoire Associe Institut National de la Recherche Agronomique d'Immunologie Parasitaire, Faculte de Pharmacie, Tours, France.
Debbabi
H
H
Mennechet
F J
FJ
Martin
V
V
Lepage
A C
AC
Schwartzman
J D
JD
Kasper
L H
LH
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