Host defense against Neospora caninum infection via IL-12p40 production through TLR2/TLR3-AKT-ERK signaling pathway in C57BL/6 mice

被引：9

作者：

Zhang, Xu ^{[1
]}

Li, Xin ^{[1
]}

Gong, Pengtao ^{[1
]}

Wang, Xiaocen ^{[1
]}

Zhang, Nan ^{[1
]}

Chen, Mengge ^{[1
]}

Zhang, Xichen ^{[1
]}

Li, Jianhua ^{[1
]}

机构：

[1] Jilin Univ, Coll Vet Med, Minist Educ, Key Lab Zoonosis Res, 5333 Xian Rd, Changchun 130062, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2021年 / 139卷

关键词：

N; caninum; IL-12p40; TLR2; TLR3-AKT-ERK; Macrophages; MONOCYTE-DERIVED MACROPHAGES; GUANYLATE-BINDING PROTEINS; IFN-GAMMA; INTERFERON-GAMMA; TOXOPLASMA-GONDII; ACTIVATION; EXPRESSION; CELLS; RECOGNITION; IMMUNITY;

D O I：

10.1016/j.molimm.2021.08.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neospora caninum is an intracellular parasite which can cause neosporosis and significant economic losses in both dairy and beef industries worldwide. A better understanding of the immune response by host cells against N. caninum could help to design better strategies for the prevention and treatment of neosporosis. Although previous studies have shown TLR2/TLR3 were involved in controlling N. caninum infection in mice, the precise mechanisms of the AKT and MAPK pathways controlled by TLR2/TLR3 to regulate N. caninum-induced IL-12p40 production and the role of TLR2/TLR3 in anti-N. caninum infection in bovine macrophages remain unclear. In the present study, TLR2-/- mice displayed more parasite burden and lower level of IL-12p40 production compared to TLR3-/- mice. N. caninum could activate AKT and ERK signaling pathways in WT mouse macrophages, which were inhibited in TLR2-/- and TLR3-/- mouse macrophages. In N. caninum-infected WT mouse macrophages, AKT inhibitor or AKT siRNA could decrease the phosphorylation of ERK. AKT or ERK inhibitors reduced the production of IL-12p40 and increased the number of parasites. The productions of ROS, NO, and GBP2 were significantly reduced in TLR2-/- and TLR3-/- mouse macrophages. Supplementation of rIL-12p40 inhibited N. caninum proliferation and rescued the productions of IFN-gamma, NO, and GBP2 in WT, TLR2-/-, and TLR3-/mouse macrophages. In bovine macrophages, the expressions of TLR2, TLR3, and IL-12p40 mRNA were significantly enhanced by N. caninum, and N. caninum proliferation was inhibited by TLR2/TLR3 agonists. Taken together, the proliferation of N. caninum in mouse macrophages was controlled by the TLR2/TLR3-AKT-ERK signal pathway via increased IL-12p40 production, which in turn lead to the productions of NO, GBP2, and IFN-gamma during N. caninum infection. And in bovine macrophages, TLR2 and TLR3 contributed to inhibiting N. caninum proliferation via increased IL-12p40 production.

引用

页码：140 / 152

页数：13

共 49 条

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