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2016 ; 113
(44
): 12526-12531
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Community deworming alleviates geohelminth-induced immune hyporesponsiveness
#MMPMID27791067
Wammes LJ
; Hamid F
; Wiria AE
; May L
; Kaisar MM
; Prasetyani-Gieseler MA
; Djuardi Y
; Wibowo H
; Kruize YC
; Verweij JJ
; de Jong SE
; Tsonaka R
; Houwing-Duistermaat JJ
; Sartono E
; Luty AJ
; Supali T
; Yazdanbakhsh M
Proc Natl Acad Sci U S A
2016[Nov]; 113
(44
): 12526-12531
PMID27791067
show ga
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. Helminth-specific 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 (P(time)) < 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
lymphocyte-associated antigen 4 (CTLA-4) on CD4(+) T cells of albendazole-treated
individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21
mo, respectively; P(time) = 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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