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Infection and Immunity, March 2001, p. 1635-1642, Vol. 69, No. 3
Laboratoire de Protozoologie, Unité de
Pathologie Aviaire et de Parasitologie, INRA de Tours, 37380 Nouzilly,
France
Received 24 July 2000/Returned for modification 30 August
2000/Accepted 12 December 2000
Both neonatal and C57BL/6 gamma interferon (IFN-
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1635-1642.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Cryptosporidium parvum-Specific Mucosal
Immune Response in C57BL/6 Neonatal and Gamma Interferon-Deficient
Mice: Role of Tumor Necrosis Factor Alpha in Protection
) knockout
(C57BL/6-GKO) mice are susceptible to Cryptosporidium
parvum, but the course of infection is different. Neonatal mice
are able to clear the parasite within 3 weeks, whereas C57BL/6-GKO
mice, depending on age, die rapidly or remain chronically infected. The
mechanism by which IFN-
leads to a protective immunity is yet poorly
understood. In order to investigate the effect of IFN-
on other
cytokines expressed in the intestinal mucosa during C. parvum infection, we studied cytokine mRNA expression in the
neonates and GKO (neonatal and adult) mice by quantitative reverse
transcription-PCR (RT-PCR) at 4 and 9 days after infection. IFN-
mRNA levels were quickly and strongly up-regulated in the mucosa of
neonatal mice. In GKO mice, the Th1-type response was dramatically
altered during the infection, whereas the mRNA expression levels of the
Th2-type cytokines interleukin 4 (IL-4) and IL-10 were increased in
both mouse models. In the absence of IFN-
, the adult knockout mice up-regulated the mRNA levels of inflammatory cytokines, such as IL-1
, IL-6, and granulocyte-macrophage colony-stimulating factor, in
the mucosa, but not tumor necrosis factor alpha (TNF-
), whereas all
these cytokines were up-regulated in the infected neonatal mice.
Further experiments indicated that injections of TNF-
into GKO adult
mice significantly reduced oocyst shedding. The results of the present
study indicate that the resolution of infection is dependent on the
expression of Th1-type cytokines in the mucosa of C57BL/6 mice and that
TNF-
may participate in the control of parasite development.
*
Corresponding author. Mailing address: Laboratoire de
Protozoologie, Unité de Pathologie Aviaire et de Parasitologie,
INRA de Tours, 37380 Nouzilly, France. Phone: (33) 02 47 42 77 67. Fax:
(33) 02 47 42 77 45. E-mail: slacroix{at}tours.inra.fr.
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