4.8 Article

Immunization with dendritic cells pulsed ex vivo with recombinant chlamydial protease-like activity factor induces protective immunity against genital Chlamydia muridarum challenge

Journal

FRONTIERS IN IMMUNOLOGY
Volume 2, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2011.00073

Keywords

Chlamydia trachomatis; dendritic cell; CPAF; UV-EB; genital infection

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Funding

  1. National Institutes of Health [1RO1AI074860]
  2. Army Research Office of the Department of Defense [W911NF-11-1-0136]

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We have shown that immunization with soluble recombinant chlamydial protease-like activity factor (rCPAF) and a T helper 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 11,10 and 1154. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN-gamma 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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