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Microbial Immunity and Vaccines

Nonpathogenic Colonization with Chlamydia in the Gastrointestinal Tract as Oral Vaccination for Inducing Transmucosal Protection

Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Craig R. Roy, Editor
Luying Wang
aThe 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Cuiming Zhu
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
cDepartment of Microbiology, University of South China, Hengyang, Hunan, China
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Tianyuan Zhang
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Qi Tian
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Nu Zhang
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Sandra Morrison
dDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Richard Morrison
dDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Min Xue
aThe 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China
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Guangming Zhong
bDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Craig R. Roy
Yale University School of Medicine
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DOI: 10.1128/IAI.00630-17
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ABSTRACT

Chlamydia has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal Chlamydia muridarum is able to induce robust transmucosal protection in mice. C. muridarum colonization in the gastrointestinal tract correlated with both a shortened course of C. muridarum genital tract infection and stronger protection against subsequent genital tract challenge infection. Mice preinoculated intragastrically with C. muridarum became highly resistant to subsequent C. muridarum infection in the genital tract, resulting in prevention of pathology in the upper genital tract. The transmucosal protection in the genital tract was rapidly induced, durable, and dependent on major histocompatibility complex (MHC) class II antigen presentation but not MHC class I antigen presentation. Although a deficiency in CD4+ T cells only partially reduced the transmucosal protection, depletion of CD4+ T cells from B cell-deficient mice completely abolished the protection, suggesting a synergistic role of both CD4+ T and B cells in the gastrointestinal C. muridarum-induced transmucosal immunity. However, the same protective immunity did not significantly affect C. muridarum colonization in the gastrointestinal tract. The long-lasting colonization with C. muridarum was restricted to the gastrointestinal tract and was nonpathogenic to either gastrointestinal or extragastrointestinal tissues. Furthermore, gastrointestinal C. muridarum did not alter the gut microbiota or the development of gut mucosal resident memory T cell responses to a nonchlamydial infection. Thus, Chlamydia may be developed into a safe and orally deliverable replicating vaccine for inducing transmucosal protection.

FOOTNOTES

    • Received 31 August 2017.
    • Returned for modification 16 October 2017.
    • Accepted 7 November 2017.
    • Accepted manuscript posted online 13 November 2017.
  • Supplemental material for this article may be found at https://doi.org/10.1128/IAI.00630-17.

  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

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Nonpathogenic Colonization with Chlamydia in the Gastrointestinal Tract as Oral Vaccination for Inducing Transmucosal Protection
Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Infection and Immunity Jan 2018, 86 (2) e00630-17; DOI: 10.1128/IAI.00630-17

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Nonpathogenic Colonization with Chlamydia in the Gastrointestinal Tract as Oral Vaccination for Inducing Transmucosal Protection
Luying Wang, Cuiming Zhu, Tianyuan Zhang, Qi Tian, Nu Zhang, Sandra Morrison, Richard Morrison, Min Xue, Guangming Zhong
Infection and Immunity Jan 2018, 86 (2) e00630-17; DOI: 10.1128/IAI.00630-17
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KEYWORDS

Chlamydia muridarum
oral inoculation
transmucosal immunity
nonpathogenic
Chlamydia
gastrointestinal infection
mucosal immunity
oral vaccines

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