Schistosoma japonicum infection induces macrophage polarization

Xu, Jiancai; Zhang, Hao; Chen, Lin; Zhang, Donghui; Ji, Minjun; Wu, Haiwei; Wu, Guan-Ling

doi:10.7555/jbr.27.20130072

Cited by 25 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In S. japonicum -infected mice, a T helper (Th)1 response is initiated early in infection followed by an interleukin (IL) 4 and IL-13-mediated dominant Th2 immune response as eggs become lodged in the host liver. At this time macrophages in the egg-induced granuloma are polarized into a M2 macrophage phenotype 7 8 . These macrophages, known as alternatively activated macrophages (AAM), contribute to the development of fibrosis, maintenance of granuloma, tissue repair, and host survival 9 10 .…”

mentioning

confidence: 99%

IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages

Peng

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Interleukin (IL)-33 is involved in T helper (Th)2-biased immune responses in mice infected with Schistosoma, but the precise mechanism remains to be elucidated. Herein, we investigated the role of IL-33 and its receptor ST2L in hepatic granuloma pathology induced by Schistosoma japonicum infection. We found that IL-33 induced the increased production of IL-5 and IL-13 from splenocytes and liver mononuclear cells (MNCs) of infected mice. The infected mice developed significantly higher number of ST2L-expressing cells in spleen and liver. Most of the ST2L-expressing cells in liver were F4/80+ macrophages, indicating the key role of macrophages in the response to IL-33. However, the liver MNCs in male-only worm infection had a poor response to IL-33, though elevated serum IL-33 was observed. ST2L+F4/80+ cells were lower in male-only worm infection than that of mixed infection. IL-33 and soluble egg antigen (SEA) upregulated ST2L expression on macrophages in vitro and ST2L-expressing macrophage displayed MHCII-CD11b+M2 phenotype. Macrophage deletion significantly attenuated IL-33-induced type 2 immunity and egg granuloma formation during S. japonicum infection. These data demonstrate that IL-33 contributes to hepatic granuloma pathology through induction of M2 macrophages during S. japonicum infection.

show abstract

mentioning

confidence: 99%

IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages

Peng

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Previous studies have identified alternative activated macrophages as a hallmark of various parasitic diseases, including filarial nematode Brugia malayi [ 10 ], Nippostrongylus brasiliensis [ 11 ], Trichinella spiralis [ 12 ], Schistosoma japonicum [ 13 ], and Heligmosomoides polygyrus [ 14 ], along with high expression of Chi3l3 and major eosinophilic infiltration. The brain inflammation of AC-infected mice was characterized by major infiltration of eosinophils and “inflammatory” macrophages (Ly-6C + CCR2 + CX3CR1 lo ) and a sharp increase in brain Chi3l3, an eosinophilic chemotactic factor also known as Chi3l3, ECF-L or Ym1.…”

Section: Discussionmentioning

confidence: 99%

“…Although AC may produce severe neurological disease, little is known about its underlying pathogenic mechanisms. It is widely assumed that type 2 immunity, a major protective mechanism against helminth infection, such as filarial nematode Brugia malayi [ 10 ], Nippostrongylus brasiliensis [ 11 ], Trichinella spiralis [ 12 ], Schistosoma japonicum [ 13 ], and Heligmosomoides polygyrus [ 14 ], is involved in the process of helminth infection. And IL-5 [ 15 , 16 ], IL-13 [ 17 ], and Eotaxin [ 18 , 19 ] are currently regarded as the common characteristics in eosinophilic infiltration-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Chi3l3: a potential key orchestrator of eosinophil recruitment in meningitis induced by Angiostrongylus cantonensis

Wan

Sun

et al. 2018

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundAngiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis.MethodsMathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection. The expression level of Chi3l3, the predicted key molecule, was verified using Western blotting and real-time quantitative PCR. Critical cell source of Chi3l3 and its relationship with eosinophils were identified with flow cytometry, immunohistochemistry, and further verified by macrophage depletion using liposomal clodronate. The role of soluble antigens of Angiostrongylus cantonensis in eosinophilic response was identified with mice airway allergy model by intranasal administration of Alternaria alternate. The relationship between Chi3l3 and IL-13 was identified with flow cytometry, Western blotting, and Seahorse Bioscience extracellular flux analyzer.ResultsWe analyzed the skewed cytokine pattern in brains of Angiostrongylus cantonensis-infected mice and found Chi3l3 to be an important molecule, which increased sharply during the infection. The percentage of inflammatory macrophages, the main source of Chi3l3, also increased, in line with eosinophils percentage in the brain. Network analysis and mathematical modeling predirect a functional association between Chi3l3 and IL-13. Further experiments verified that the soluble antigen of Angiostrongylus cantonensis induce brain eosinophilic meningitis via aggravating a positive feedback loop between IL-13 and Chi3l3.ConclusionsWe present evidences in favor of a key role for macrophave-derived Chi3l3 molecule in the infection of Angiostrongylus cantonensis, which aggravates eosinophilic meningitis induced by Angiostrongylus cantonensis via a IL-13-mediated positive feedback loop. These reported results constitute a starting point for future research of angiostrongyliasis pathogenesis and imply that targeting chitinases and chitinase-like-proteins may be clinically beneficial in Angiostrongylus cantonensis-induced eosinophilic meningitis.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1071-2) contains supplementary material, which is available to authorized users.

show abstract

“…The granulomatous immune response is also characterized by complicated cells, such as macrophages, which account for approximately 30% of granuloma cells [ 48 , 49 ]. A previous study showed that IFN-γ, the product of Th1 cells and acting predominantly on macrophages to drive M1 differentiation, which secret various pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-12, and activate the adaptive immune response [ 50 ]. High levels of IL-4 and IL-13, which can be secreted primarily by type-2 immune cells such as Th2 cells to act toward the alternative activation of macrophages into the M2 phenotype [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study showed that IFN-γ, the product of Th1 cells and acting predominantly on macrophages to drive M1 differentiation, which secret various pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-12, and activate the adaptive immune response [ 50 ]. High levels of IL-4 and IL-13, which can be secreted primarily by type-2 immune cells such as Th2 cells to act toward the alternative activation of macrophages into the M2 phenotype [ 50 , 51 ]. Our in vitro study suggested that the increased M2 macrophages polarization induced by fucoidan was probably due to the enhanced Th2 cells, while the declined M1 macrophages related to the decreased Th1 cells.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica

Bai

Wang

et al. 2020

Parasites Vectors

View full text Add to dashboard Cite

Background Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma japonicum infection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweed Fucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. Methods We evaluated the hepatic pathology from S. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in the S. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detected in vitro. Furthermore, macrophages were treated with fucoidan in vitro and to detect the inflammatory cytokines. Results Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response during S. japonicum infection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treated S. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treated S. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-β were dramatically increased in the livers from S. japonicum-infected mice after fucoidan treatment. Furthermore, in vitro stimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. Conclusions These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress of S. japonicum infection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.

show abstract

Schistosoma japonicum infection induces macrophage polarization

Cited by 25 publications

References 30 publications

IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages

IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages

Chi3l3: a potential key orchestrator of eosinophil recruitment in meningitis induced by Angiostrongylus cantonensis

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica

Contact Info

Product

Resources

About