Brain proteomic differences between wild-type and CD44- mice induced by chronic Toxoplasma gondii infection
- 157 Downloads
Chronic clinical Toxoplasma gondii (T. gondii) infection is the primary disease state that causes severe encephalitis. CD44 is a member of the cell adhesion molecule family and plays an important role in T. gondii infection. However, proteomic changes in CD44 during chronic T. gondii infection have rarely been reported. Thus, an iTRAQ-based proteomic study coupled with 2D-LC-MS/MS analysis was performed to screen CD44-related proteins during chronic T. gondii infection. As a result, a total of 2612 proteins were reliably identified and quantified. Subsequently, 259, 106, and 249 differentially expressed proteins (DEPs) were compared between CD44- mice (A) vs wild-type mice (B), B vs wild-type mice infected with T. gondii (C), and C vs CD44- mice infected with T. gondii (D). Gene ontology, KEGG pathway, and protein-protein interaction analyses were performed on the DEPs. According to the results, immune-related proteins were altered significantly among the A vs B, B vs C, and C vs D comparisons, which might indicate that chronic T. gondii infection caused changes in the host immune response. Additionally, Ca2+- and metabolism-related proteins were upregulated in C vs D, which supported the hypothesis that CD44 mediated the production of host Ca2+ and IFN-γ and that the parasite preferentially invaded cells expressing high levels of CD44. The present findings validate and enable a more comprehensive knowledge of the role of CD44 in hosts chronically infected with T. gondii, thus providing new ideas for future studies on the specific functions of CD44 in latent toxoplasmosis.
KeywordsToxoplasma gondii CD44- iTRAQ Proteomic Differentially expressed protein (DEP)
This work was supported by the National Natural Science Foundation of China (R.F., No. 31572510), the Natural Science Foundation of Hubei Province (Grant No. 2017CFA020), and Da Bei Nong Group Promoted Project for Young Scholar of HZAU (Grant No. 2017DBN001).
Compliance with ethical standards
The authors declare that they have no competing interests.
- Blume M, Nitzsche R, Sternberg U, Gerlic M, Masters SL, Gupta N, McConville MJ (2015) A Toxoplasma gondii gluconeogenic enzyme contributes to robust central carbon metabolism and is essential for replication and virulence. Cell Host Microbe 18:210–220. https://doi.org/10.1016/j.chom.2015.07.008 CrossRefPubMedGoogle Scholar
- Egan ES, Jiang RHY, Moechtar MA, Barteneva NS, Weekes MP, Nobre LV, Gygi SP, Paulo JA, Frantzreb C, Tani Y, Takahashi J, Watanabe S, Goldberg J, Paul AS, Brugnara C, Root DE, Wiegand RC, Doench JG, Duraisingh MT (2015) Malaria. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion. Science 348:711–714. https://doi.org/10.1126/science.aaa3526 CrossRefPubMedPubMedCentralGoogle Scholar
- Foger N, Marhaba R, Zoller M (2000) CD44 supports T cell proliferation and apoptosis by apposition of protein kinases. Eur J Immunol 30:2888–2899. https://doi.org/10.1002/1521-4141(200010)30:10<2888::AID-IMMU2888>3.0.CO;2–4Google Scholar
- Freitas do Rosario AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, Muller W, O'Garra A, Langhorne J (2012) IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. J Immunol 188:1178–1190. https://doi.org/10.4049/jimmunol.1102755 CrossRefPubMedGoogle Scholar
- Gee K, Lim W, Ma W, Nandan D, Diaz-Mitoma F, Kozlowski M, Kumar A (2002) Differential regulation of CD44 expression by lipopolysaccharide (LPS) and TNF-alpha in human monocytic cells: distinct involvement of c-Jun N-terminal kinase in LPS-induced CD44 expression. J Immunol 169:5660–5672CrossRefPubMedGoogle Scholar
- Gitau EN, Kokwaro GO, Newton CRJC, Ward SA (2011) Global proteomic analysis of plasma from mice infected with Plasmodium berghei ANKA using two dimensional gel electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. Malar J 10:Artn 205. https://doi.org/10.1186/1475-2875-10-205 CrossRefGoogle Scholar
- Jurzynski C, Gysin J, Pouvelle B (2007) CD44, a signal receptor for the inhibition of the cytoadhesion of CD36-binding Plasmodium falciparum-infected erythrocytes by CSA-binding infected erythrocytes. Microbes Infect 9:1463–1470. https://doi.org/10.1016/j.micinf.2007.07.011 CrossRefPubMedGoogle Scholar
- Li C, Wu Y, Orian-Rousseau V, Zhang Y, Gulbins E, Grassme H (2017) Regulation of Staphylococcus aureus infection of macrophages by CD44, reactive oxygen species and acid sphingomyelinase. Antioxid Redox Signal. https://doi.org/10.1089/ars.2017.6994
- Mahmoudvand H, Saedi Dezaki E, Soleimani S, Baneshi MR, Kheirandish F, Ezatpour B, Zia-Ali N (2015) Seroprevalence and risk factors of Toxoplasma gondii infection among healthy blood donors in south-east of Iran. Parasite Immunol 37:362–367. https://doi.org/10.1111/pim.12198 CrossRefPubMedGoogle Scholar
- Mercier A, Ajzenberg D, Devillard S, Demar MP, de Thoisy B, Bonnabau H, Collinet F, Boukhari R, Blanchet D, Simon S, Carme B, Dardé ML (2011) Human impact on genetic diversity of Toxoplasma gondii: example of the anthropized environment from French Guiana. Infect Genet Evol 11:1378–1387. https://doi.org/10.1016/j.meegid.2011.05.003 CrossRefPubMedGoogle Scholar
- Ohshima J, Lee Y, Sasai M, Saitoh T, Su Ma J, Kamiyama N, Matsuura Y, Pann-Ghill S, Hayashi M, Ebisu S, Takeda K, Akira S, Yamamoto M (2014) Role of mouse and human autophagy proteins in IFN-gamma-induced cell-autonomous responses against Toxoplasma gondii. J Immunol 192:3328–3335. https://doi.org/10.4049/jimmunol.1302822 CrossRefPubMedGoogle Scholar
- Singleton PA, Bourguignon LY (2004) CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation. Exp Cell Res 295:102–118. https://doi.org/10.1016/j.yexcr.2003.12.025 CrossRefPubMedGoogle Scholar
- Wong NKY, Lai JCY, Maeshima N, Johnson P (2011) CD44-mediated elongated T cell spreading requires Pyk2 activation by Src family kinases, extracellular calcium, phospholipase C and phosphatidylinositol-3 kinase. Cell Signal 23:812–819. https://doi.org/10.1016/j.cellsig.2011.01.003 CrossRefPubMedGoogle Scholar