Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge

We have shown that immunization with soluble recombinant (r) chlamydial protease-like activity factor (rCPAF) and a T helper (Th) 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study,...

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Main Authors: Bernard eArulanandam, Weidang eLi, Ashlesh eMurthy, Bharatkumar eChaganty, M N Guentzel, janakiram eseshu, James Patrick Chambers, Guangming eZhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2011-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00073/full
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author Bernard eArulanandam
Weidang eLi
Ashlesh eMurthy
Bharatkumar eChaganty
M N Guentzel
janakiram eseshu
James Patrick Chambers
Guangming eZhong
author_facet Bernard eArulanandam
Weidang eLi
Ashlesh eMurthy
Bharatkumar eChaganty
M N Guentzel
janakiram eseshu
James Patrick Chambers
Guangming eZhong
author_sort Bernard eArulanandam
collection DOAJ
description We have shown that immunization with soluble recombinant (r) chlamydial protease-like activity factor (rCPAF) and a T helper (Th) 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs) pulsed ex vivo with rCPAF+CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF+CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40 and major histocompatibility complex class II (MHC II), and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN- and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.
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spelling doaj.art-7723cc81eff741629a0b57663da96e572022-12-21T18:47:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-12-01210.3389/fimmu.2011.0007316683Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum ChallengeBernard eArulanandam0Weidang eLi1Ashlesh eMurthy2Bharatkumar eChaganty3M N Guentzel4janakiram eseshu5James Patrick Chambers6Guangming eZhong7University of Texas as San AntonioUniversity of Texas as San AntonioMidwestern UniversityUniversity of Texas as San AntonioUniversity of Texas as San AntonioUniversity of Texas as San AntonioUniversity of Texas as San AntonioUniversity of Texas Health Science CenterWe have shown that immunization with soluble recombinant (r) chlamydial protease-like activity factor (rCPAF) and a T helper (Th) 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs) pulsed ex vivo with rCPAF+CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF+CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40 and major histocompatibility complex class II (MHC II), and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN- and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00073/fullChlamydia trachomatisVaccinationCPAFDenditic CellsGenital Pathology
spellingShingle Bernard eArulanandam
Weidang eLi
Ashlesh eMurthy
Bharatkumar eChaganty
M N Guentzel
janakiram eseshu
James Patrick Chambers
Guangming eZhong
Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
Frontiers in Immunology
Chlamydia trachomatis
Vaccination
CPAF
Denditic Cells
Genital Pathology
title Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
title_full Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
title_fullStr Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
title_full_unstemmed Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
title_short Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge
title_sort immunization with dendritic cells pulsed ex vivo with recombinant chlamydial protease like activity factor induces protective immunity against genital chlamydia muridarum challenge
topic Chlamydia trachomatis
Vaccination
CPAF
Denditic Cells
Genital Pathology
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00073/full
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