Expression of Genes Encoding Th1 Cell-Activating Cytokines and Lymphoid Homing Chemokines by Chlamydia-Pulsed Dendritic Cells Correlates with Protective Immunizing Efficacy

Abstract

We studied the expression of cytokines, chemokines, and chemokine receptors by the RNase protection assay in chlamydia-pulsed dendritic cells to better understand their potent anti-chlamydial immunizing properties. We found that chlamydia-pulsed dendritic cells express a complex profile of inflammatory and immunomodulatory molecules. These include CCR-7, interleukin-12, and interferon-induced protein 10, molecules that might influence the homing of pulsed dendritic cells to the site of chlamydial infection and the induction of a local protective CD4 ؉ Th1 cellular immunity.Chlamydia trachomatis is an obligatory intracellular bacterial parasite that infects the oculogenital mucosal epithelium, causing trachoma, the world's leading cause of preventable blindness, and sexually transmitted diseases. Pelvic inflammatory disease is a serious sequalae of C. trachomatis infection of the female genital tract that can result in tubal blockage, infertility, or ectopic pregnancy (2,4,8,13). The development of an efficacious vaccine against C. trachomatis oculogenital infection is likely to be key to the control of both trachoma and chlamydial sexually transmitted diseases. Despite considerable effort, however, there has been little favorable progress toward this end. Conventional vaccination approaches have produced disappointing results in their abilities to prevent infection of the mouse female genital tract (12,14,19), despite a modicum of success in controlling chlamydial infection of the respiratory tract (20). Solid protective immunity to genital rechallenge has been achieved only by infection or adoptive immunization with dendritic cells (DC) pulsed ex vivo with inactivated whole chlamydial organisms (6, 18). Interestingly, mice immunized with chlamydia-pulsed DC exhibit equivalent levels of protective immunity to that in mice that have spontaneously resolved a primary genital infection (18). Both infection-mediated protective immunity and immunity elicited following adoptive transfer of antigen-pulsed DC correlate with a chlamydia-specific CD4ϩ Th1-biased immune response characterized by the secretion of high levels of gamma interferon from local and splenic CD4ϩ T cells (6,18). Recent studies have also indicated an important cooperative role for both CD4 ϩ T cells and B cells in recall immunity in the murine model; however the mechanism(s) that mediates this cooperative effector function has not been described (11). Clearly, the use of ex vivo antigenpulsed DC as a practical chlamydial vaccine is unsuited for use in humans. Nevertheless, the ability of ex vivo antigen-pulsed DC to elicit solid antichlamydial protective immunity at the genital mucosae is gratifying because it demonstrates that a more complete understanding of chlamydia-DC interactions may provide important information applicable to the development of a conventional antichlamydial vaccine.In this work we have investigated cytokine, chemokine, and chemokine receptor gene expression in chlamydia-pulsed DC by the RNase protection assay (RPA). Our findin...

Hematopoietic Cells Are Required to Initiate a Chlamydia trachomatis-Specific CD8+ T Cell Response

“…Su et al (54) demonstrated that the adoptive transfer of bone marrow-derived DCs pulsed ex vivo with nonviable C. trachomatis induced protective immunity comparable to that induced by live C. trachomatis infection. The use of nonviable C. trachomatis naturally focused this and later studies on the CD4 ϩ T cell response to C. trachomatis (55). The CD8 ϩ T cell response remained unobserved in these studies because cytosolic localization of protein Ags was thought to be required for stimulating CD8…”

Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis

“…[34][35][36][37] Antigen-pulsed mature DCs express genes that induce DCs migration, activation and recruitment of T cells, 37 and different antigens phagocytosed by DCs induce different patterns of cytokine production by CD4 þ T cells, depending on the cytokines produced by the DCs. 34 The availability of DC-derived IL-12 is a requirement for the development of protective immunity.…”

NK Cells Promote Type 1 T Cell Immunity through Modulating the Function of Dendritic Cells during Intracellular Bacterial Infection

“…A recent study showed that NK cells can enhance the capacity of DC to present parasitic Ags via the NKG2D receptor pathway (21). The important role of DC in initiation and maintenance of T cell responses to chlamydial infection has been demonstrated by several previous studies using mouse models of C. trachomatis mouse pneumonitis strain, more recently called Chlamydia muridarum (22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Su et al (22) reported that i.v.…”