Abstract
Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. Alternative activated macrophages (M2) as well as Treg cells, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite. The precise mechanism by which helminths modulate host immune response is not fully understood. To determine the functions of parasite-induced M2 macrophages, we compared the effects of M1 and M2 macrophages obtained from Trichinella spiralis-infected mice with those of T. spiralis excretory/secretory (ES) protein-treated macrophages on experimental intestinal inflammation and allergic airway inflammation. T. spiralis infection induced M2 macrophage polarization by increasing the expression of CD206, ARG1, and Fizz2. In a single application, we introduced macrophages obtained from T. spiralis-infected mice and T. spiralis ES protein-treated macrophages into mice tail veins before the induction of dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-alum sensitization, and OVA challenge. Colitis severity was assessed by determining the severity of colitis symptoms, colon length, histopathologic parameters, and Th1-related inflammatory cytokine levels. Compared with the DSS-colitis group, T. spiralis-infected mice and T. spiralis ES protein-treated macrophages showed significantly lower disease activity index (DAI) at sacrifice and smaller reductions of body weight and proinflammatory cytokine level. The severity of allergic airway inflammation was assessed by determining the severity of symptoms of inflammation, airway hyperresponsiveness (AHR), differential cell counts, histopathologic parameters, and levels of Th2-related inflammatory cytokines. Severe allergic airway inflammation was induced after OVA-alum sensitization and OVA challenge, which significantly increased Th2-related cytokine levels, eosinophil infiltration, and goblet cell hyperplasia in the lung. However, these severe allergic symptoms were significantly decreased in T. spiralis-infected mice and T. spiralis ES protein-treated macrophages. Helminth infection and helminth ES proteins induce M2 macrophages. Adoptive transfer of macrophages obtained from helminth-infected mice and helminth ES protein-activated macrophages is an effective treatment for preventing and treating airway allergy in mice and is promising as a therapeutic for treating inflammatory diseases.
Highlights
Macrophage activation can be generally divided into two distinct categories: classically activated macrophages (M1) and alternatively activated macrophages (AAM, M2)
To determine which type of macrophage was activated during T. spiralis infection, the expression levels of M1 and M2 marker including CD11c. inducible nitric oxide synthase (iNOS) (M1 marker), and CD206, Argninase 1 (Arg1) (M2 marker) were evaluated in macrophages obtained from peritoneium of T. spiralis-infected mice at 2 weeks post infection (PI)
The results demonstrate that ES protein treatment increased IRF4 and STAT6 expression related to M2 macrophages polarization
Summary
Macrophage activation can be generally divided into two distinct categories: classically activated macrophages (M1) and alternatively activated macrophages (AAM, M2). M2b macrophages are induced upon combine exposure to IC and TLR agonist or by IL-1R agonists and express high level s of TNF superfamily 14 and CCL1 These cells express and secrete high levels of the anti-inflammatory cytokine IL-10 and low levels of IL-22, which is the function al converse of M1 macrophages. Our previous study demonstrated that Trichinella spiralis infection derived Treg cells were the key cells mediating the amelioration of allergic airway inflammation and DSS-induced colitis in mice[35,36] Infection with parasites such as Brugia malayi and Schistosoma mansoni triggers M2 macrophages[37,38,39,40,41]. These findings clearly indicate the important role of macrophages in the alleviation of inflammation[45,46,47,48,49]
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