Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Rα in vitro

Du, Linlin; Wei, Haiyan; Li, Leiqing; Shan, Hui; Yang, Yu; Wang, Yesong; Zhang, Gensheng

doi:10.1016/j.cellimm.2014.01.010

Cited by 30 publications

(29 citation statements)

References 32 publications

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“…Previous studies have demonstrated that helminth infections or the treatment with their ES products led to significant M1-to-M2 macrophage transition, which is dependent on activation of the STAT6 signaling (25,48). Studies using STAT6 knockout mice also demonstrated a defect in M2-associated responses in helminth infections (23).…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with recombinant Trichinella spiralis-specific 53-kDa glycoprotein (rTsP53) showed a preventive effect on trinitrobenzene sulfonic acid-induced colitis by evoking an M2-bias innate immunity and stimulating Th2 responses in our previous study (24). Furthermore, in an in vitro study, rTsP53 showed anti-inflammatory function by inducing M2 macrophages via acting dependently on STAT6 (25). Recently, vaccination with recombinant Trichinella spiralis cathepsin B-like protein (rTsCPB) cloned/expressed by our team also showed an IgG1 (Th2)-prone response in mice (26).…”

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confidence: 92%

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Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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“…Several studies have indicated that excretory-secretory (ES) products, particularly the 53-kDa protein TsP53 from T. spiralis, attenuate experimental colitis and the LPS-induced damage from endotoxemia in mice and also induce macrophage activation to M2 (24)(25)(26). TsP53-induced M2 macrophage activation is reported to be STAT6 dependent but not IL-4R␣ independent.…”

Section: Discussionmentioning

confidence: 99%

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

Asano

Srinontong

et al. 2016

Infect Immun

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cInfectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-␥)-dependent Ab production was not due to a decrease in IFN-␥ production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b ؉ spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation.T richinella species are parasitic nematodes for many mammalian hosts, including humans (1). After the ingestion of muscle tissues contaminated with the muscle larval form of Trichinella, the larvae develop into adult worms by molting in the small intestine of the host. Female adult worms invade the intestinal tissue to release newborn larvae. Newborn larvae systemically migrate in the host body to striated muscle cells, resulting in survival for many years (2). Trichinella are thought to establish long-term parasitism by escaping elimination through alterations in host immune responses (3, 4). There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis and T. britovi) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). Although both types of Trichinella survive in the host muscle tissues for long periods of time, the strategies for their survival may be different. Indeed, the infected host mounts an immune response to the infection with both types of Trichinella, but each immune response is different, possibly due to the different forms of immunomodulation shown by each Trichine...

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“…Treatment of peritoneal macrophages with a recombinant of 53-kDa protein derived from T. spiralis brought about expression of mannose receptor, a novel mammalian lectin (Ym1), arginase-1, and IL-10, hallmarks of M2 phenotype. This effect was independent of IL-4Rα, but dependent on STAT6 (76). …”

Section: M2-type Of Macrophage Response Without Help Of Th2 Cytokinesmentioning

confidence: 99%

Evolutionary Roots of Arginase Expression and Regulation

Dzik

2014

Front. Immunol.

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Two main types of macrophage functions are known: classical (M1), producing nitric oxide, NO, and M2, in which arginase activity is primarily expressed. Ornithine, the product of arginase, is a substrate for synthesis of polyamines and collagen, important for growth and ontogeny of animals. M2 macrophages, expressing high level of mitochondrial arginase, have been implicated in promoting cell division and deposition of collagen during ontogeny and wound repair. Arginase expression is the default mode of tissue macrophages, but can also be amplified by signals, such as IL-4/13 or transforming growth factor-β (TGF-β) that accelerates wound healing and tissue repair. In worms, the induction of collagen gene is coupled with induction of immune response genes, both depending on the same TGF-β-like pathway. This suggests that the main function of M2 “heal” type macrophages is originally connected with the TGF-β superfamily of proteins, which are involved in regulation of tissue and organ differentiation in embryogenesis. Excretory–secretory products of metazoan parasites are able to induce M2-type of macrophage responses promoting wound healing without participation of Th2 cytokines IL-4/IL-13. The expression of arginase in lower animals can be induced by the presence of parasite antigens and TGF-β signals leading to collagen synthesis. This also means that the main proteins, which, in primitive metazoans, are involved in regulation of tissue and organ differentiation in embryogenesis are produced by innate immunity. The signaling function of NO is known already from the sponge stage of animal evolution. The cytotoxic role of NO molecule appeared later, as documented in immunity of marine mollusks and some insects. This implies that the M2-wound healing promoting function predates the defensive role of NO, a characteristic of M1 macrophages. Understanding when and how the M1 and M2 activities came to be in animals is useful for understanding how macrophage immunity, and immune responses operate.

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Regulation of recombinant Trichinella spiralis 53-kDa protein (rTsP53) on alternatively activated macrophages via STAT6 but not IL-4Rα in vitro

Cited by 30 publications

References 32 publications

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses

Evolutionary Roots of Arginase Expression and Regulation

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