Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy

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 o...

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Bibliographic Details
Published in:The Journal of clinical investigation 2000-10, Vol.106 (8), p.1053-1060
Main Authors: Borkow, G, Leng, Q, Weisman, Z, Stein, M, Galai, N, Kalinkovich, A, Bentwich, Z
Format: Article
Language:English
Subjects:
Abatacept
Antigens, CD
Antigens, Differentiation
CD28 Antigens
CD4-CD8 Ratio
Chemokines, CC
Chronic Disease
Clonal Anergy
CTLA-4 Antigen
Ethiopia - ethnology
Helminthiasis - immunology
Humans
Hypersensitivity, Delayed
Immunoconjugates
Immunologic Memory
Intestinal Diseases, Parasitic - immunology
Israel - epidemiology
Mitogen-Activated Protein Kinases - metabolism
Phytohemagglutinins
Protein-Tyrosine Kinases - metabolism
Signal Transduction
T-Lymphocytes - immunology
Tetradecanoylphorbol Acetate
Tuberculin Test
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Summary: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.
ISSN:0021-9738
DOI:10.1172/JCI10182