Abstract
BackgroundThe recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.Methodology/Principal FindingsWe compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.Conclusion/Significance T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.
Highlights
In humans, trichinellosis, caused by oral infection with Trichinella sp., is typified by an intestinal phase and a muscular phase, corresponding to two distinct periods in the parasite’s life cycle in the host [1,2]
Many studies have investigated the down-regulation of the immune system by parasite infection
Our previous study suggested that Treg cells recruited by Trichinella spiralis infection were the key cells mediating the amelioration of allergic airway inflammation in mice
Summary
Trichinellosis, caused by oral infection with Trichinella sp., is typified by an intestinal phase and a muscular phase, corresponding to two distinct periods in the parasite’s life cycle in the host [1,2]. During each of the two phases, the host immune system activates different responses to the infection. Th2-related cytokine levels increase immediately after T. spiralis larvae invade the intestine [4], and the levels of IL-4 and IL-13 peak before the initiation of nurse cell formation [4,5]. The levels of most Th17-related cytokines increase until the muscle phase begins. Th2- and Th17related cytokine levels decrease after the recruitment of CD4+CD25+ Forkhead box P3 (Foxp3)+T (Treg) cells to the spleen and lymph nodes [4]. Treg cells appear to play a role in the maintenance of chronic infections or in the suppression of the parasite targeting immune response [4,6]. The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system
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