Intranasal immunization with recombinant Toxoplasma gondii actin depolymerizing factor confers protective efficacy against toxoplasmosis in mice

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Abstract

Background

Toxoplasma gondii is an opportunistic protozoan closely associated with AIDS and vertical transmission. T. gondii actin depolymerizing factor (TgADF) plays an important role in actin cytoskeleton remodeling, and it is required to invade host cells. TgADF was a promising vaccine candidate. To observe the immunological changes and protective efficacy of recombinant TgADF protein (rTgADF) against T. gondii infection, we optimized the intranasal immunization dose of rTgADF and analyzed the survival rate and tachyzoite loads in mouse tissues after oral challenge with T. gondii tachyzoites.

Results

rTgADF was prepared, purified, and combined with mouse anti-His antibody and rabbit anti- T. gondii serum. After intranasal immunization with 10 μg, 20 μg, 30 μg, or 40 μg of rTgADF, the 30-μg group elicited high levels of secretory IgA (sIgA) in nasal, intestinal, and vesical washes, raised IgG titres in the sera, strong proliferation of splenocytes, and increased secretion of IL-2 and IFN-γ when compared with the control group. When the mice were orally challenged with T. gondii, an increase in the survival rate (36.36 %) and a decrease in the tachyzoite loads in the liver (67.77 %) and brain (51.01 %) were observed.

Conclusions

Our findings demonstrate that intranasal immunization with rTgADF can simultaneously trigger mucosal and systemic immune responses and protect the mice against T. gondii infection.

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Most cited references 33

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The history of Toxoplasma gondii--the first 100 years.

Jitender Dubey (2015)

In this paper the history of Toxoplasma gondii and toxoplasmosis is reviewed. This protozoan parasite was first discovered in 1908 and named a year later. Its medical importance remained unknown until 1939 when T. gondii was identified in tissues of a congenitally infected infant, and veterinary importance became known when it was found to cause abortion storms in sheep in 1957. The discovery of a T. gondii specific antibody test, Sabin-Feldman dye test in 1948 led to the recognition that T. gondii is a common parasite of warm-blooded hosts with a worldwide distribution. Its life cycle was not discovered until 1970 when it was found that felids are its definitive host and an environmentally resistant stage (oocyst) is excreted in feces of infected cats. The recent discovery of its common infection in certain marine wildlife (sea otters) indicates contamination of our seas with T. gondii oocysts washed from land. Hygiene remains the best preventive measure because currently there is no vaccine to prevent toxoplasmosis in humans.

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Foodborne toxoplasmosis.

Helen Jones, Jitender Dubey (2012)

Toxoplasmosis can be due to congenital infection or acquired infection after birth and is one of the leading illnesses associated with foodborne hospitalizations and deaths. Undercooked meat, especially pork, lamb, and wild game meat, and soil contaminated with cat feces on raw fruits and vegetables are the major sources of foodborne transmission for humans. The new trend in the production of free-range organically raised meat could increase the risk of Toxoplasma gondii contamination of meat. Foodborne transmission can be prevented by production practices that reduce T. gondii in meat, adequate cooking of meat, washing of raw fruits and vegetables, prevention of cross contamination in the kitchen, and measures that decrease spread of viable oocysts into the environment.

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B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii.

Peter G Gibson, Peter Sayles, Tanya Johnson (2000)

T lymphocytes and gamma interferon (IFN-gamma) are known mediators of immune resistance to Toxoplasma gondii infection, but whether B cells also play an important role is not clear. We have investigated this issue using B-cell-deficient (muMT) mice. If vaccinated with attenuated T. gondii tachyzoites, muMT mice are susceptible to a challenge intraperitoneal infection with highly virulent tachyzoites that similarly vaccinated B-cell-sufficient mice resist. Susceptibility is evidenced by increased numbers of parasites at the challenge infection site and by extensive mortality. The susceptibility of B-cell-deficient mice does not appear to be caused by deficient T-cell functions or diminished capacity of vaccinated and challenged B-cell-deficient mice to produce IFN-gamma. Administration of Toxoplasma-immune serum, but not nonimmune serum, to vaccinated B-cell-deficient mice significantly prolongs their survival after challenge with virulent tachyzoites. Vaccinated mice lacking Fc receptors or the fifth component of complement resist a challenge infection, suggesting that neither Fc-receptor-dependent phagocytosis of antibody-coated tachyzoites nor antibody-dependent cellular cytotoxicity nor antibody-and-complement-dependent lysis of tachyzoites is a crucial mechanism of resistance. However, Toxoplasma-immune serum effectively inhibits the infection of host cells by tachyzoites in vitro. Together, the results support the hypothesis that B cells are required for vaccination-induced resistance to virulent tachyzoites in order to produce antibodies and that antibodies may function protectively in vivo by blocking infection of host cells by tachyzoites.

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Author and article information

Contributors

Zhuanzhuan Liu: liouzhuanzhuan12@163.com

Litian Yin: yinlitian@gmail.com

Yaqing Li: 793044993@qq.com

Fei Yuan: yuanfei0910@163.com

Xiaofan Zhang: zxiaofanwin@163.com

Jiazhi Ma: 1056617031@qq.com

Hongmei Liu: Liuhmm163@163.com

Yanjuan Wang: wangyanjuan1036@126.com

Kuiyang Zheng: ZKY02@163.com

Jianping Cao: caojp@yahoo.com

Journal

Journal ID (nlm-ta): BMC Immunol

Journal ID (iso-abbrev): BMC Immunol

Title: BMC Immunology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2172

Publication date (Electronic): 6 October 2016

Publication date PMC-release: 6 October 2016

Publication date Collection: 2016

Volume: 17

Electronic Location Identifier: 37

Affiliations

[1 ]Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, Jiangsu 221004 People’s Republic of China

[2 ]Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001 People’s Republic of China

[3 ]National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory of Parasite and Vector Biology, MOH, China; National Center for International Research on Tropical Diseases, China; WHO Collaborating Center for Tropical Diseases, Shanghai, 200025 People’s Republic of China

[4 ]School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510000 People’s Republic of China

Article

Publisher ID: 173

DOI: 10.1186/s12865-016-0173-9

PMC ID: 5053087

PubMed ID: 27716047

SO-VID: ca6f0f87-85bb-44d2-ad38-842c44090d4d

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 14 July 2016

Date accepted : 20 September 2016

Funding

Funded by: the Laboratory of Parasite and Vector Biology, MOH, China

Award ID: WSBKTKT201402

Award Recipient : Zhuanzhuan Liu

Funded by: the National Natural Science Foundation

Award ID: 81371841

Award Recipient : Jianping Cao

Funded by: the Natural Science Foundation of Shandong Province, China

Award ID: ZR2014YL031

Award Recipient : Zhuanzhuan Liu

Custom metadata

ScienceOpen disciplines: Immunology

Keywords: toxoplasma gondii,toxoplasmosis,actin depolymerizing factor,intranasal immunization

Data availability:

ScienceOpen disciplines: Immunology

Keywords: toxoplasma gondii, toxoplasmosis, actin depolymerizing factor, intranasal immunization

Intranasal immunization with recombinant Toxoplasma gondii actin depolymerizing factor confers protective efficacy against toxoplasmosis in mice

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Abstract

Background

Results

Conclusions

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Gamma Delta T cells

Most cited references 33

The history of Toxoplasma gondii--the first 100 years.

Foodborne toxoplasmosis.

B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii.

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