The Proinflammatory Cytokine Response toChlamydia trachomatisElementary Bodies in Human Macrophages Is Partly Mediated by a Lipoprotein, the Macrophage Infectivity Potentiator, through TLR2/TLR1/TLR6 and CD14

Abstract

Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1β, TNF-α, IL-6, and IL-8. rMip proinflammatory activity could not be attributed to Escherichia coli LPS contamination as determined by the Limulus Amoebocyte lysate assay, insensitivity to polymyxin B (50 μg/ml), and different serum requirement. We have recently demonstrated that Mip is a “classical” bacterial lipoprotein, exposed at the surface of EB. The proinflammatory activity of EB was significantly attenuated in the presence of polyclonal Ab to rMip. Native Mip was able to induce TNF-α and IL-8 secretion, whereas a nonlipidated C20A rMip variant was not. Proinflammatory activity of rMip was unaffected by heat or proteinase K treatments but was greatly reduced by treatment with lipases, supporting a role of lipid modification in this process. Stimulating pathways appeared to involve TLR2/TLR1/TLR6 with the help of CD14 but not TLR4. These data support a role of Mip lipoprotein in pathogenesis of C. trachomatis-induced inflammatory responses.

Role of Oxidative Stress and Chlamydia trachomatis in Infertile Women with Anti-Zona Pellucida Autoantibodies

“…A significant serum level of AZP-Ab (20.8%) was reported among infertility cases without any detectable level in fertile control. Our results are quite different from those reported the presence of anti-zona pellucida activities in the sera of fertile female [22,23]. The presence of anti-zona activity in infertile women may be an autoimmune response, possibly due to absorption and degradation of the ova into the peritoneal cavity or in the reproductive tract and the subsequent exposure of the degradation products to the immune system [24].…”

“…IgG antibodies in serum were the best predictor of a current or potential past Chlamydia infection. Host immune response plays important roles in the pathogenesis of long-term complications after Chlamydia infections [22,24] statistically significantly incidence of ASA and AZP-Ab in the serum and cervical secretion. An early investigations for immunological and bacteriological factors associated with female infertility provides an important diagnostic and prognostic information, decrease the probability of tubal damage and might prevent further complication of infertility.…”

Safety and efficacy of anti–tumor necrosis factor α therapy in ten patients with recent‐onset refractory reactive arthritis

“…The best documented of these is the class I major histocompatibility complex molecule HLA-B27. The persistence of the bacteria triggers the host's innate (4) and adaptive (5) immune responses. Local and systemic overproduction of cytokines contributes to the pathogenesis of the disease.…”

Role of Chlamydia in the Development of Ocular Adnexal Lymphoma

“…Chlamydia PAMPs such as Hsp-60 and Macrophage Infectivity Potentiator lipoprotein (MIP) are recognized by host PRR TLR4 and TLR2 respectively. These host receptors selectively recognize a broad spectrum of microbial components and endogenous molecules released by injured tissue [45]. In particular, TLR4 and TLR2 have been reported to be essential mediators of C. pneumoniae related host cell activation and defense and MyD88, the central TLR signaling adaptor molecule during Chlamydial infections, is crucial for the initiation of effective host defenses induced by recognition of C. pneumoniae by TLRs [46].…”