Adoptive transfer of Trichinella spiralis-activated macrophages can ameliorate both Th1- and Th2-activated inflammation in murine models

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 T reg 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.

Th2 signals are not essential for the anti‐arthritic effects of Trichinella spiralis in mice

“…Trichinella sp infection or their products protect experimental hosts from several immune diseases 25 such as type 1 diabetes (T1D) in NOD mice, 26 inflammatory bowel diseases (IBD), [27][28][29][30][31][32][33][34] experimental autoimmune encephalomyelitis (EAE) 35,36 and adjuvant arthritis. 37 Regarding other helminths, Th2 signals were reported to be essential for the anti-arthritic effects.…”

Trichinella spiralis:inflammation modulator

“…Trichinella spiralis infection inhibits epithelial and crypt cell destruction and sustains mast cell stabilization, which prevents mucosal mast cell hyperplasia and exacerbates motor responses against intestinal inflammation (Serna et al, 2006). ES products from adult T. spiralis (AES) alleviate IBD with acute inflammatory colonic disease in mice induced by dextran sodium sulphate, which was mediated by inhibition of Th1/Th17 proinflammatory cytokines and an increase in the production of anti-inflammatory Th2/Treg regulatory cytokines in the lymphocytes of colon, mesenteric lymph node and spleen of mice treated with AES (Yang et al, 2014;Kang et al, 2019). Motomura et al (2009) showed Fig.…”

“…Molecules released by T. spiralis Trichinella spiralis can survive for long periods in the host, and this is mediated by the parasite's ability to modulate the host immune response through the secretion of immunomodulatory molecules (Yang et al, 2013;Liu et al, 2014;Sun et al, 2015;Tang et al, 2015;Cvetkovic et al, 2016;Guo et al, 2016) (table 2). ES products released by the different life stages of T. spiralis are involved in acute inflammatory responses and modulate molecular cross-talk between the parasite and host (Sun et al, 2011;Kang et al, 2019).…”

A novel cystatin derived from Trichinella spiralis suppresses macrophage-mediated inflammatory responses

“…Treatment of J774A.1 or RAW264.7 macrophage cell lines with TsES significantly reduced the expression of LPS-induced pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and IL-12 but increased the expression of regulatory cytokine; this effect was observed even in the presence of ES products alone [5,6]. Adoptive transfer of macrophages obtained from T. spiralis-infected mice or TsES-treated macrophages into colitis or airway hyperresponsiveness (AHR) mouse models could ameliorate disease severity [7]. Although there have been several studies demonstrating TsES immunomodulatory capacity, few have focused on the characterization of effective molecules, and many of these molecules need to be further identified.…”