2016-11-01
Community deworming alleviates geohelminth-induced immune hyporesponsiveness
Publication
Publication
Proceedings of the National Academy of Sciences of the United States of America , Volume 113 - Issue 44 p. 12526- 12531
In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminthspecific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 mo - estimate [95% confidence interval], 0.37 [0.21-0.53], P value over time (Ptime) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) on CD4+ T cells of albendazoletreated individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21 mo, respectively; Ptime = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low- compared with high-income countries.
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doi.org/10.1073/pnas.1604570113, hdl.handle.net/1765/94105 | |
Proceedings of the National Academy of Sciences of the United States of America | |
Organisation | Department of Medical Microbiology and Infectious Diseases |
Wammes, L.J. (Linda J.), Hamid, F. (Firdaus), Wiria, A.E. (Aprilianto Eddy), May, L. (Linda), Kaisar, M.M.M. (Maria M.M.), Prasetyani-Gieseler, M.A. (Margaretta A.), … Yazdanbakhsh, M. (2016). Community deworming alleviates geohelminth-induced immune hyporesponsiveness. In Proceedings of the National Academy of Sciences of the United States of America (Vol. 113, pp. 12526–12531). doi:10.1073/pnas.1604570113 |