This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Graham, S. P.
Right arrow Articles by Bianco, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Graham, S. P.
Right arrow Articles by Bianco, A. E.
Right arrowPubmed/NCBI databases
*Substance via MeSH

 Previous Article  |  Next Article 

Infection and Immunity, July 2001, p. 4313-4319, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4313-4319.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Down-Regulated Lymphoproliferation Coincides with Parasite Maturation and with the Collapse of Both Gamma Interferon and Interleukin-4 Responses in a Bovine Model of Onchocerciasis†

Simon P. Graham,1,* Alexander J. Trees,1 Robert A. Collins,2 Davina M. Moore,1 Francis M. Guy,1 Mark J. Taylor,1 and Albert E. Bianco1

Liverpool School of Tropical Medicine, Liverpool L3 5QA,1 and Institute for Animal Health, Compton, Newbury RG20 7NN,2 United Kingdom

Received 12 December 2000/Returned for modification 6 February 2001/Accepted 12 April 2001

Onchocerciasis is a debilitating parasitic infection caused by the filarial nematode Onchocerca volvulus. Infections are chronic, and persistence of the parasites for several years argues for highly adapted mechanisms of immune evasion. Due to the restricted host repertoire of O. volvulus, we have used the cattle parasite Onchocerca ochengi to investigate the nature of immunomodulation underpinning these long-term infections. Cattle were infected with a single inoculation of 350 infective-stage larvae under laboratory conditions (n = 6). Intradermal nodules containing immature adult worms were detected from 110 days postinfection, and microfilariae in skin were detected from day 280 postinfection. Parasite-specific responses during early infection were nonpolarized with respect to the major Th cytokines (interleukin-4 [IL-4], IL-2, and gamma interferon [IFN-gamma ]) produced by antigen-stimulated peripheral blood mononuclear cells (PBMC) or serum antibody isotypes. Antigen-induced proliferation of PBMC peaked shortly after exposure and remained high during the prepatent infection. As the parasites matured and animals developed patent infections, there was a profound down-regulation of lymphoproliferation, accompanied by sharp falls in the expression of both IL-4 and IFN-gamma and a gradual decline in IL-2. Levels of immunoglobulin G2 (IgG2) fell, while those of IgG1 remained high. We conclude that neither a classical Th2 response nor a simple Th1-to-Th2 switch is sufficient to explain the immunomodulation associated with patent Onchocerca infections. Instead, there is an initial Th0 response, which matures into a response with some, but not all of the features of a Th2 response. The natural host-parasite relationship of O. ochengi in cattle may be useful as both a descriptive and predictive tool to test more refined models of immunomodulation in onchocerciasis.

* Corresponding author. Present address: International Livestock Research Institute, P.O. Box 30709, Nairobi Kenya. Phone: 254-2 630743. Fax: 254-2 631499. E-mail: sgraham{at}cgiar.org.

dagger We are sad to report the death of R.A.C. shortly before completion of the manuscript.

Infection and Immunity, July 2001, p. 4313-4319, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4313-4319.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dondji, B., Bungiro, R. D., Harrison, L. M., Vermeire, J. J., Bifulco, C., McMahon-Pratt, D., Cappello, M. (2008). Role for Nitric Oxide in Hookworm-Associated Immune Suppression. Infect. Immun. 76: 2560-2567 [Abstract] [Full Text]  
  • Hise, A. G., Daehnel, K., Gillette-Ferguson, I., Cho, E., McGarry, H. F., Taylor, M. J., Golenbock, D. T., Fitzgerald, K. A., Kazura, J. W., Pearlman, E. (2007). Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM. J. Immunol. 178: 1068-1076 [Abstract] [Full Text]  
  • NFON, C. K., MAKEPEACE, B. L., NJONGMETA, L. M., TANYA, V. N., TREES, A. J. (2007). LACK OF RESISTANCE AFTER RE-EXPOSURE OF CATTLE CURED OF ONCHOCERCA OCHENGI INFECTION WITH OXYTETRACYCLINE. Am J Trop Med Hyg 76: 67-72 [Abstract] [Full Text]  
  • Taylor, M. D., Harris, A., Nair, M. G., Maizels, R. M., Allen, J. E. (2006). F4/80+ Alternatively Activated Macrophages Control CD4+ T Cell Hyporesponsiveness at Sites Peripheral to Filarial Infection.. J. Immunol. 176: 6918-6927 [Abstract] [Full Text]  
  • Tchakoute, V. L., Graham, S. P., Jensen, S. A., Makepeace, B. L., Nfon, C. K., Njongmeta, L. M., Lustigman, S., Enyong, P. A., Tanya, V. N., Bianco, A. E., Trees, A. J. (2006). In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination. Proc. Natl. Acad. Sci. USA 103: 5971-5976 [Abstract] [Full Text]  
  • Babu, S., Nutman, T. B. (2003). Proinflammatory Cytokines Dominate the Early Immune Response to Filarial Parasites. J. Immunol. 171: 6723-6732 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»