Abstract
Helminths regulate host immune responses to ensure their own long-term survival. Numerous studies have demonstrated that these helminth-induced regulatory mechanisms can also limit host inflammatory responses in several disease models. We used the Heligmosomoides bakeri (Hb) infection model (also known as H. polygyrus or H. polygyrus bakeri in the literature) to test whether such immune regulation affects skin inflammatory responses induced by the model contact sensitiser dibutyl phthalate fluorescein isothiocynate (DBP-FITC). Skin lysates from DBP-FITC-sensitized, Hb-infected mice produced less neutrophil specific chemokines and had significantly reduced levels of skin thickening and cellular inflammatory responses in tissue and draining lymph nodes (LNs) compared to uninfected mice. Hb-induced suppression did not appear to be mediated by regulatory T cells, nor was it due to impaired dendritic cell (DC) activity. Mice cleared of infection remained unresponsive to DBP-FITC sensitization indicating that suppression was not via the secretion of Hb-derived short-lived regulatory molecules, although long-term effects on cells cannot be ruled out. Importantly, similar helminth-induced suppression of inflammation was also seen in the draining LN after intradermal injection of the ubiquitous allergen house dust mite (HDM). These findings demonstrate that Hb infection attenuates skin inflammatory responses by suppressing chemokine production and recruitment of innate cells. These findings further contribute to the growing body of evidence that helminth infection can modulate inflammatory and allergic responses via a number of mechanisms with potential to be exploited in therapeutic and preventative strategies in the future.
Highlights
Various epidemiological studies have drawn a link between the incidence of helminth infection and reduction in allergic and inflammatory diseases [1,2,3,4]
We sought to determine the effect of chronic helminth infection on skin inflammatory responses by infecting mice with Heligmosomoides bakeri (Hb) 14 days prior to sensitization with DBPFITC
To determine whether the effect of Hb infection on the DBP-FITC-induced inflammatory response was dependent on the presence of live worms secreting biologically active molecules, we used ivermectin to clear mice of adult worms and measured the subsequent DBP-FITC-induced skin inflammation and lymph nodes (LNs) hyperplasia
Summary
Various epidemiological studies have drawn a link between the incidence of helminth infection and reduction in allergic and inflammatory diseases [1,2,3,4]. In seeking mechanisms by which this might occur, experimental models have linked helminth-induced regulatory T and B cells (Tregs and Bregs, respectively), to the dampening of responses to allergens [5, 6] such as HDM [7, 8], ovalbumin (OVA) [9, 10] and peanut [11], and to the amelioration of inflammation in a number of disease models including colitis [12,13,14], experimental autoimmune encephalitis [15], and diabetes [16, 17]. Macrophages from Trichinella spiralis-infected donors, or those treated with T. spiralis excretory-secretory (ES) products in vitro, were found to be protective in models of colitis and OVA-induced allergic airway inflammation when transferred into recipient mice [19]. Chronic infection with Litomosoides sigmodontis protects mice from OVA-induced anaphylaxis by decreasing numbers and activity of mast cells [22]
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