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PMID: 11032865 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 106 ·No. 8 ·2000-10-00 ·Pages 1053-60

Borkow G, Leng Q, Weisman Z, Stein M, Galai N, Kalinkovich A, Bentwich Z

Abstract

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.

MeSH Terms
Abatacept Antigens, CD Antigens, Differentiation CD28 Antigens CD4-CD8 Ratio CTLA-4 Antigen Chemokines, CC Chronic Disease Clonal Anergy 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
Chemicals
Antigens, CD Antigens, Differentiation CD28 Antigens CTLA-4 Antigen CTLA4 protein, human Chemokines, CC Immunoconjugates Phytohemagglutinins Abatacept Protein-Tyrosine Kinases Mitogen-Activated Protein Kinases Tetradecanoylphorbol Acetate
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Borkow G
R. Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot, Israel.
Leng Q
Weisman Z
Stein M
Galai N
Kalinkovich A
Bentwich Z
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI10182
Published
2000-10-00
Pages
1053-60
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC314342
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI10182 PMC Full Text View journal details
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