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Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy
Open accessAbstract
Helminthic parasites cause widespread, persistent infections in humans. The immigration of Ethiopians to Israel (a group denoted here by "Eth."), many of them infested with helminths and in a chronic immune-activation state, enabled us to investigate the effects of such immune activation on immune responses. We studied the immune profile and immune functions of 190 Eth. and Israeli non-Eth. (Isr.) highly, partially, or non-immune-activated individuals. Immune cells from highly immune-activated individuals were defective in several signaling responses, all of which were restored gradually following anti-helminthic treatment. These cells showed poor transmembrane signaling, as seen by the phosphorylation of various tyrosine kinases and of the MAPK kinases, ERK1/2 and p38; deficient degradation of phosphorylated IkappaBalpha; increased expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), which appears to block proliferative responses in these cells; decreased beta-chemokine secretion by CD8(+) cells after stimulation; and reduced proliferation to recall antigen stimulation. Highly immune-activated individuals also showed decreased delayed-type skin hypersensitivity responses to recall antigen before deworming. These findings support the notion that chronic helminthic infections cause persistent immune activation that results in hyporesponsiveness and anergy. Such impaired immune functions may diminish the capacity of these individuals to cope with infections and to generate cellular protective immunity after vaccination.
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Citations
Cited by
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Bousquet, J., Khaltaev, N., Cruz, A. A., Denburg, J., Fokkens, W. J., Togias, A., Zuberbier, T., Baena‐Cagnani, C. E., Canonica, G. W., Van Weel, C., et al. (2008) · Allergy · doi:10.1111/j.1398-9995.2007.01620.x · Cited by 4,729
Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision
Brożek, J. L., Bousquet, J., Baena-Cagnani, C. E., Bonini, S., Canonica, G. W., Casale, T. B., van Wijk, R. G., Ohta, K., Zuberbier, T., & Schünemann, H. J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.06.047 · Cited by 1,813
Helminth parasites – masters of regulation
Maizels, R. M., Balic, A., Gomez‐Escobar, N., Nair, M., Taylor, M. D., & Allen, J. E. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00191.x · Cited by 866
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Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial
Summers, R. W., Elliott, D. E., Urban, J. F., Thompson, R. A., & Weinstock, J. V. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.01.005 · Cited by 613
Metadata
- Authors
- Borkow, G., Leng, Q., Weisman, Z., Stein, M., Galai, N., Kalinkovich, A., & Bentwich, Z.
- Venue
- Journal of Clinical Investigation
- Published
- 2000-10-15
- Volume
- 106
- Issue
- 8
- Pages
- 1053-1060
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2153811068
- Cited by
- 218
- References
- 0
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Borkow, G., Leng, Q., Weisman, Z., Stein, M., Galai, N., Kalinkovich, A., & Bentwich, Z. (2000). Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. Journal of Clinical Investigation. https://doi.org/10.1172/jci10182
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