Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>

ABSTRACT Microneme (MIC) proteins play important roles in the recognition, adhesion, and invasion of host cells by Toxoplasma gondii. Previous studies have shown that MIC proteins are highly immunogenic in the mouse and recognized by human serum antibodies. Here we report that T. gondii antigens MIC...

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Autores principales:	Iti Saraav, Qiuling Wang, Kevin M. Brown, L. David Sibley
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	antigen-specific T cells gamma interferon detection assays memory T cells microneme antigens recall response toxoplasmosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f39f027f8e634a85b411915e3d234755
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spelling	oai:doaj.org-article:f39f027f8e634a85b411915e3d2347552021-11-15T15:22:04ZSecretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>10.1128/mSphere.00711-182379-5042https://doaj.org/article/f39f027f8e634a85b411915e3d2347552019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00711-18https://doaj.org/toc/2379-5042ABSTRACT Microneme (MIC) proteins play important roles in the recognition, adhesion, and invasion of host cells by Toxoplasma gondii. Previous studies have shown that MIC proteins are highly immunogenic in the mouse and recognized by human serum antibodies. Here we report that T. gondii antigens MIC1, MIC3, MIC4, and MIC6 were capable of inducing memory responses leading to production of gamma interferon (IFN-γ) by T cells from T. gondii-infected mice. Production of IFN-γ was demonstrated using enzyme-linked immunosorbent spot (ELISPOT) assay and also intracellular cytokine staining. All four MIC antigens displayed very high sensitivity (100%) and specificity (86 to 100%) for detecting chronic infection. Interestingly, IFN-γ was produced by both CD4+ and CD8+ T cells in BALB/c mice but primarily by CD4+ T cells in C57BL/6 mice. Phenotypic characterization of IFN-γ-producing CD4+ and CD8+ T cells in BALB/c mice and CD4+ T cells in C57BL/6 mice revealed effector memory T cells (CD44hi CD62Llo) as the predominant cells that contributed to IFN-γ production in response to MIC antigens. Effector memory responses were seen in mice of different major histocompatibility complex class II (MHC-II) haplotypes, suggesting that MIC antigens contain epitopes that are broadly recognized. IMPORTANCE Current diagnosis of toxoplasmosis relies almost exclusively on antibody detection, and while detection of IgG provides a useful estimate of prior infection, it does not alone indicate immune status. In contrast, detection of IFN-γ responses to T. gondii antigens has been used to monitor immune responsiveness in HIV-infected patients, thus providing valuable predictions about the potential for disease reactivation. However, specific T. gondii antigens that can be used in assays to detect cellular immunity remain largely undefined. In this study, we examined the diagnostic potential of microneme antigens of T. gondii using IFN-γ detection assays. Our findings demonstrate that MIC antigens (MIC1, MIC3, MIC4, and MIC6) elicit IFN-γ responses from memory T cells in chronically infected mice. Monitoring IFN-γ production by T cells stimulated with MIC antigens provided high sensitivity and specificity for detection of T. gondii infection in mice. Taken together, these studies suggest that microneme antigens might be useful as an adjunct to serological testing to monitor immune status during infection.Iti SaraavQiuling WangKevin M. BrownL. David SibleyAmerican Society for Microbiologyarticleantigen-specific T cellsgamma interferon detection assaysmemory T cellsmicroneme antigensrecall responsetoxoplasmosisMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	antigen-specific T cells gamma interferon detection assays memory T cells microneme antigens recall response toxoplasmosis Microbiology QR1-502
spellingShingle	antigen-specific T cells gamma interferon detection assays memory T cells microneme antigens recall response toxoplasmosis Microbiology QR1-502 Iti Saraav Qiuling Wang Kevin M. Brown L. David Sibley Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
description	ABSTRACT Microneme (MIC) proteins play important roles in the recognition, adhesion, and invasion of host cells by Toxoplasma gondii. Previous studies have shown that MIC proteins are highly immunogenic in the mouse and recognized by human serum antibodies. Here we report that T. gondii antigens MIC1, MIC3, MIC4, and MIC6 were capable of inducing memory responses leading to production of gamma interferon (IFN-γ) by T cells from T. gondii-infected mice. Production of IFN-γ was demonstrated using enzyme-linked immunosorbent spot (ELISPOT) assay and also intracellular cytokine staining. All four MIC antigens displayed very high sensitivity (100%) and specificity (86 to 100%) for detecting chronic infection. Interestingly, IFN-γ was produced by both CD4+ and CD8+ T cells in BALB/c mice but primarily by CD4+ T cells in C57BL/6 mice. Phenotypic characterization of IFN-γ-producing CD4+ and CD8+ T cells in BALB/c mice and CD4+ T cells in C57BL/6 mice revealed effector memory T cells (CD44hi CD62Llo) as the predominant cells that contributed to IFN-γ production in response to MIC antigens. Effector memory responses were seen in mice of different major histocompatibility complex class II (MHC-II) haplotypes, suggesting that MIC antigens contain epitopes that are broadly recognized. IMPORTANCE Current diagnosis of toxoplasmosis relies almost exclusively on antibody detection, and while detection of IgG provides a useful estimate of prior infection, it does not alone indicate immune status. In contrast, detection of IFN-γ responses to T. gondii antigens has been used to monitor immune responsiveness in HIV-infected patients, thus providing valuable predictions about the potential for disease reactivation. However, specific T. gondii antigens that can be used in assays to detect cellular immunity remain largely undefined. In this study, we examined the diagnostic potential of microneme antigens of T. gondii using IFN-γ detection assays. Our findings demonstrate that MIC antigens (MIC1, MIC3, MIC4, and MIC6) elicit IFN-γ responses from memory T cells in chronically infected mice. Monitoring IFN-γ production by T cells stimulated with MIC antigens provided high sensitivity and specificity for detection of T. gondii infection in mice. Taken together, these studies suggest that microneme antigens might be useful as an adjunct to serological testing to monitor immune status during infection.
format	article
author	Iti Saraav Qiuling Wang Kevin M. Brown L. David Sibley
author_facet	Iti Saraav Qiuling Wang Kevin M. Brown L. David Sibley
author_sort	Iti Saraav
title	Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_short	Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full	Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_fullStr	Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full_unstemmed	Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_sort	secretory microneme proteins induce t-cell recall responses in mice chronically infected with <named-content content-type="genus-species">toxoplasma gondii</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/f39f027f8e634a85b411915e3d234755
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Secretory Microneme Proteins Induce T-Cell Recall Responses in Mice Chronically Infected with <named-content content-type="genus-species">Toxoplasma gondii</named-content>

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