Ascaris lumbricoides Cystatin Prevents Development of Allergic Airway Inflammation in a Mouse Model

Abstract

Severe helminth infections are negatively associated to allergic diseases like asthma; therefore, the immunomodulatory properties of parasite-derived components have been analyzed, raising the possibility of their use as anti-inflammatory molecules. We evaluated the immunomodulatory properties of Ascaris lumbricoides recombinant cysteine protease inhibitor (rAl-CPI) in a mouse model of allergic airway inflammation induced by the house dust mite (HDM) Blomia tropicalis and its effects on human monocyte-derived dendritic cells (HmoDCs). The B. tropicalis sensitized/challenged mice developed extensive cellular airway inflammatory response, which was significantly reduced upon treatment with rAl-CPI prior to B. tropicalis sensitization, affecting particularly the perivascular/peribronchial infiltrate cells, eosinophils/neutrophils, and goblet cells. A significant decrease of Th2 cytokines, total, and specific IgE antibodies was observed in rAl-CPI treated mice. The antibody response was biased to IgG, mainly IgG2a. Administration of rAl-CPI-alone and rAl-CPI before mite sensitization were associated with a significant increase of regulatory T cells (Tregs) in spleen and elevated IL-10 levels in BAL and splenocytes culture supernatants, which was partially affected by anti-IL10 receptor use. In vitro, rAl-CPI showed a modulatory effect on HmoDCs, lowering the expression of HLA-DR, CD83, and CD86, while inducing IL-10 and IL-6 production. This suggests an inhibition of HmoDC maturation and a possible link with the inhibition of the allergic response observed in the murine model.

Protective action of N-stearoylethanolamine on blood coagulation and arterial changes in spontaneously hypertensive rats fed cholesterol-rich diet

“…Fibrinogen is the acute phase protein whose concentration increases during inflammation. Also, fibrinogen synthesis is increased under the action of interleukin-6 [26,27]. In our studies, animals treated with CRD showed elevated fibrinogen levels that completely corresponded to those reported in the literature.…”

What Can Parasites Tell Us About the Pathogenesis and Treatment of Asthma and Allergic Diseases

“…Cystatin from N. brasiliensis (NbCys) dampened OVA-specific splenocyte proliferation, as well as IgE and cytokine production by inhibiting cathepsins L and B (89). Similar effects were observed for cystatin (rAl-CPI) from A. lumbricoides, which decreased T H 2 cytokine and IgE production in a mouse model of HDM-induced AAI (92).…”

“…Mammalian cysteine proteases are required for proteolytic processing of antigens, enabling presentation on MHC class II molecules and effective T cell responses. Cystatins from A. viteae, Brugia malayi, N. brasiliensis, Onchocerca volvulus, Clonorchis sinensis, A. lumbricoides, H. polygyrus, and Litomosoides sigmodontis have been shown to interfere with this process to evade antigen-induced immunity (83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94). AvCystatin from A. viteae mitigated airway inflammation and colitis in mice through the induction of IL-10-producing macrophages (93) and reduced pollen-specific responses in lymphocytes from allergic patients (94).…”

Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes

“…Likewise, it was shown that they lead to a weaker antigen-specific antibody response as an untreated control (30). In a mouse model displaying allergic airway inflammation responding to house dust mite, it was shown that CPI from Ascaris lumbricoides (AlCPI), one of the most common parasitic worms found in humans, especially affects perivascular infiltrating cells, eosinophils, neutrophils and goblet cells in the lung and reduces Th2 cytokines (31). Also, a distinct shift from IgE antibodies to IgG, mostly IgG2a, was reported.…”