Helminth infection modulates systemic pro-inflammatory cytokines and chemokines implicated in type 2 diabetes mellitus pathogenesis

PLoS Negl Trop Dis. 2020 Mar 3;14(3):e0008101. doi: 10.1371/journal.pntd.0008101. eCollection 2020 Mar.

Abstract

Background: The prevalence of helminth infections exhibits an inverse association with the prevalence of Type 2 diabetes mellitus (T2DM), and helminths are postulated to mediate a protective effect against T2DM. However, the biological mechanism behind this effect is not known.

Aims/methods: We postulated that helminth infections act by modulating the pro-inflammatory cytokine and chemokine milieu that is characteristic of T2DM. To examine the association of cytokines and chemokines in helminth-diabetes co-morbidity, we measured the plasma levels of a panel of pro-inflammatory cytokines and chemokines in individuals with Strongyloides stercoralis infection (Ss+) and T2DM at the time of Ss diagnosis and then 6 months after definitive anthelmintic treatment along with uninfected control individuals with T2DM alone (Ss-).

Principal findings: Ss+ individuals exhibited significantly diminished levels of the pro-inflammatory cytokines-IL-1α, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-27, G-CSF and GM-CSF and chemokines-CCL1, CCL2, CCL3, CCL11, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10 and CXCL11. In contrast, Ss+ individuals exhibited significantly elevated levels of IL-1Ra. Anthelmintic treatment resulted in increased levels of all of the cytokines and chemokines.

Conclusions: Thus, helminth infections alleviate and anthelmintic therapy partially restores the plasma cytokine and chemokine levels in helminth-diabetes co-morbidity. Our data therefore offer a plausible biological mechanism for the protective effect of helminth infections against T2DM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Anthelmintics / administration & dosage*
  • Cytokines / blood*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / prevention & control
  • Female
  • Humans
  • Male
  • Middle Aged
  • Strongyloides stercoralis / immunology*
  • Strongyloidiasis / drug therapy*
  • Strongyloidiasis / pathology*
  • Young Adult

Substances

  • Anthelmintics
  • Cytokines