A Double‐Edged Sword: Complement Component 3 in <i>Toxoplasma gondii</i> Infection

Huang, Wanyi; Wang, Ya‐Pei; Mahmmod, Yasser S.; Wang, Junjie; Liu, Tanghui; Zheng, Yanhua; Zhou, Xue; Zhang, Xiu‐Xiang; Yuan, Zihao

doi:10.1002/pmic.201800271

Cited by 11 publications

(12 citation statements)

References 110 publications

(151 reference statements)

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“…In addition, C4A has been associated with roles in schizophrenia (Liesmaa et al, 2018;Melbourne et al, 2018;Prasad et al, 2018;Ji et al, 2019). While complement activation has been previously demonstrated in the brain during Toxoplasma infection, the common functions of C4A point toward a possible role in increasing vascular permeability gradually during chronic infection for the continued infiltration of peripheral immune cells into the brain (Xiao et al, 2016;Huang et al, 2019). Interestingly, BALB/c mice experience significantly less expression of C4A at each infection time point compared to C57BL/ 6 mice which is an indication that there is decreased vascular permeability in these mice compared to B6.…”

Section: Discussionmentioning

confidence: 99%

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Bergersen

Barnes

Worth

et al. 2021

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is a resilient parasite that infects a multitude of warm-blooded hosts and results in a lifelong chronic infection requiring continuous responses by the host. Chronic infection is characterized by a balanced immune response and neuropathology that are driven by changes in gene expression. Previous research pertaining to these processes has been conducted in various mouse models, and much knowledge of infection-induced gene expression changes has been acquired through the use of high throughput sequencing techniques in different mouse strains and post-mortem human studies. However, lack of infection time course data poses a prominent missing link in the understanding of chronic infection, and there is still much that is unknown regarding changes in genes specifically relating to neuropathology and resulting repair mechanisms as infection progresses throughout the different stages of chronicity. In this paper, we present a targeted approach to gene expression analysis during T. gondii infection through the use of NanoString nCounter gene expression assays. Wild type C57BL/6 and BALB/c background mice were infected, and transcriptional changes in the brain were evaluated at 14, 28, and 56 days post infection. Results demonstrate a dramatic shift in both previously demonstrated and novel gene expression relating to neuropathology and resolution in C57BL/6 mice. In addition, comparison between BALB/c and C57BL/6 mice demonstrate initial differences in gene expression that evolve over the course of infection and indicate decreased neuropathology and enhanced repair in BALB/c mice. In conclusion, these studies provide a targeted approach to gene expression analysis in the brain during infection and provide elaboration on previously identified transcriptional changes and also offer insights into further understanding the complexities of chronic T. gondii infection.

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Section: Discussionmentioning

confidence: 99%

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Bergersen

Barnes

Worth

et al. 2021

Front. Cell. Infect. Microbiol.

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“…These changes were associated with neurodegeneration ( Li et al, 2019 ). An avirulent Toxoplasma strain also caused upregulation of complement proteins, including C3, C4b, and C1q, in the mouse brain ( Huang et al, 2019 ). Furthermore, mRNAs for FB and FP, C3aR, and C5aR were up-regulated in the brain of mice chronically infected with an avirulent Toxoplasma strain ( Shinjyo et al, 2021 ), suggesting that the alternative pathway is activated in the brain during chronic infection.…”

Section: Interactions Between Infectious Agents and Complement In The Cnsmentioning

confidence: 99%

“…In Toxoplasma-infected brain, complement components (C3, C4b, and C1q) were upregulated possibly causing the disruption of tight junctions. Huang et al, 2019 3 (in vivo) Persistent infection model: Type I T. gondii (GT1) in mice (5 months post infection)…”

Section: Study Design Outcomes Conclusion Referencesmentioning

confidence: 99%

Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia

Shinjyo

Kagaya

Pekna

2021

Front. Cell. Neurosci.

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As part of the innate immune system, complement plays a critical role in the elimination of pathogens and mobilization of cellular immune responses. In the central nervous system (CNS), many complement proteins are locally produced and regulate nervous system development and physiological processes such as neural plasticity. However, aberrant complement activation has been implicated in neurodegeneration, including Alzheimer’s disease. There is a growing list of pathogens that have been shown to interact with the complement system in the brain but the short- and long-term consequences of infection-induced complement activation for neuronal functioning are largely elusive. Available evidence suggests that the infection-induced complement activation could be protective or harmful, depending on the context. Here we summarize how various infectious agents, including bacteria (e.g., Streptococcus spp.), viruses (e.g., HIV and measles virus), fungi (e.g., Candida spp.), parasites (e.g., Toxoplasma gondii and Plasmodium spp.), and prion proteins activate and manipulate the complement system in the CNS. We also discuss the potential mechanisms by which the interaction between the infectious agents and the complement system can play a role in neurodegeneration and dementia.

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“…It has been proved that T. gondii can recruit C4BP and factor H from the host, inactivate the surface-bound C3 and limit C5b-9 from forming a membrane attack complex [ 17 , 18 ], eventually resulting in immune escape. It was reported that the complement pathway and tight junction (TJ) pathway have specific changes in mouse brain tissues because of the significant increase in C3 expression led by T. gondii infection [ 19 ]. C3 may be related to the process of T. gondii entering the host brain.…”

Section: Introductionmentioning

confidence: 99%

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii

et al. 2022

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Background: Toxoplasma gondii, an intracellular protozoan parasite, exists in the host brain as cysts, which can result in Toxoplasmic Encephalitis (TE) and neurological diseases. However, few studies have been conducted on TE, particularly on how to prevent it. Previous proteomics studies have showed that the expression of C3 in rat brains was up-regulated after T. gondii infection. Methods: In this study, we used T. gondii to infect mice and bEnd 3 cells to confirm the relation between T. gondii and the expression of C3. BEnd3 cells membrane proteins which directly interacted with C3a were screened by pull down. Finally, animal behavior experiments were conducted to compare the differences in the inhibitory ability of TE by four chemotherapeutic compounds (SB290157, CVF, NSC23766, and Anxa1). Results: All chemotherapeutic compounds in this study can inhibit TE and cognitive behavior in the host. However, Anxa 1 is the most suitable material to inhibit mice TE. Conclusion: T. gondii infection promotes TE by promoting host C3 production. Anxa1 was selected as the most appropriate material to prevent TE among four chemotherapeutic compounds closely related to C3.

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A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection

Cited by 11 publications

References 110 publications

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii

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