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

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. Author summary: Helminth infections are postulated to provide a degree of protection against the development of metabolic disorders such as T2DM and alleviate pathology following development of such disorders. However, the biological mechanism underlying this interaction is largely unknown. Since pro-inflammatory cytokines and chemokines are major drivers of pathology in T2DM, we examined the influence of coexistent helminth infection (in this case, Strongyloides stercoralis) on the cytokine and chemokine milieu in T2DM. We demonstrate that helminth infection significantly alleviates the pro-inflammatory milieu in T2DM by lowering the systemic levels of cytokines and chemokines. We also demonstrate that anthelmintic therapy exacerbates this pro-inflammatory milieu by partially restoring the high levels of cytokines and chemokines. So, our data uncovers a role for cytokines and chemokines in the mainstream interaction between helminth infections and metabolic disorders.