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Infection and Immunity, August 2003, p. 4580-4585, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4580-4585.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interleukin-4 and Transforming Growth Factor ß Have Opposing Regulatory Effects on Gamma Interferon-Mediated Inhibition of Cryptosporidium parvum Reproduction

I.-Sarah Lean, Stuart A. C. McDonald, Mona Bajaj-Elliott,{dagger} Richard C. G. Pollok,{ddagger} Michael J. G. Farthing,§ and Vincent McDonald*

Department of Adult and Paediatric Gastroenterology, Barts, and the London School of Medicine, London, United Kingdom

Received 14 February 2003/ Returned for modification 1 April 2003/ Accepted 19 May 2003

It was shown previously that enterocytes activated by gamma interferon (IFN-{gamma}) are efficient effector cells in the killing of Cryptosporidium parvum. How this function is regulated is not clearly understood, but transforming growth factor ß (TGF-ß) and the Th2 regulatory cytokines may play a role. Using an in vitro cell culture system, we investigated how the key regulatory cytokines interleukin-4 (IL-4), IL-10, IL-13, and TGF-ß might modulate the effect of IFN-{gamma} in inducing resistance to infection in enterocyte cell lines. The results showed that TGF-ß can abolish the inhibitory effect on C. parvum development and that neither IL-13 nor IL-10 influenced the action of IFN-{gamma}. In contrast, IL-4 cooperated with low concentrations of IFN-{gamma} (1 and 10 U/ml) to enhance parasite killing. One mechanism that appeared to be involved in the combined activity of IFN-{gamma} and IL-4 was intracellular Fe2+ deprivation, but induction of nitric oxide production was not involved. In one cell line, the extents and durations of phosphorylation of STAT1, a transcription factor involved in IFN-{gamma} signaling, were similar when cells were stimulated with IFN-{gamma} alone and with IFN-{gamma} and IL-4{gamma}, suggesting that the cooperative effect of the cytokines was not related to STAT1 activation. The effects of the presence of TGF-ß and IL-4 on IFN-{gamma} function did not appear to involve any alteration in the level of expression of IFN-{gamma} receptors.

* Corresponding author. Mailing address: Department of Adult and Paediatric Gastroenterology, DDRC, Barts, and the London School of Medicine and Dentistry, Turner St., London E1 2AD, United Kingdom. Phone: 44 020 7882 7191. Fax: 44 020 7882 7192. E-mail: v.mcdonald{at}qmul.ac.uk.

Editor: J. M. Mansfield

{dagger} Present address: Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children Trust and the Institute of Child Health, London WC1 N1EH, United Kingdom.

{ddagger} Present address: Department of Gastroenterology, St. George's Hospital, Tooting, London SW17 0QT, United Kingdom.

§ Present address: Office of Executive Dean, University of Glasgow, Glasgow G12 8LG, United Kingdom.

Infection and Immunity, August 2003, p. 4580-4585, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4580-4585.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Takeuchi, D., Jones, V. C., Kobayashi, M., Suzuki, F. (2008). Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected with Cryptosporidium parvum. Infect. Immun. 76: 3657-3663 [Abstract] [Full Text]  
  • Lean, I-S., Lacroix-Lamande, S., Laurent, F., McDonald, V. (2006). Role of Tumor Necrosis Factor Alpha in Development of Immunity against Cryptosporidium parvum Infection. Infect. Immun. 74: 4379-4382 [Abstract] [Full Text]  


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