Ureaplasma parvum lipoproteins, including MB antigen, activate NF-{kappa}B through TLR1, TLR2 and TLR6

Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Microbiology (Impact Factor: 2.84). 06/2008; 154(Pt 5):1318-25. DOI: 10.1099/mic.0.2007/016212-0
Source: PubMed

ABSTRACT Ureaplasma species (Ureaplasma parvum and Ureaplasma urealyticum) are commonly isolated pathogens from the female reproductive tract and are associated with perinatal diseases in humans. Inappropriate induction of inflammatory responses may be involved in the occurrence of such diseases; however, pathogenic agents that induce the inflammatory response have not been identified in ureaplasmas. In this study, we examined the involvement of Toll-like receptors (TLRs) in the activation of the immune response by U. parvum lipoproteins, as well as the U. parvum components responsible for nuclear factor kappaB (NF-kappaB) activation. The Triton X-114 (TX-114) detergent phase of U. parvum was found to induce NF-kappaB through TLR2. The active components of the TX-114 detergent phase were lipoproteins, such as multiple banded (MB) antigen, UU012 and UU016 of U. parvum. The activation of NF-kappaB by these lipoproteins was inhibited by dominant negative (DN) constructs of TLR1 and DN TLR6. Thus, the lipoproteins from U. parvum were found to activate NF-kappaB through TLR1, TLR2 and TLR6. Furthermore, these lipoproteins possessed an ability to induce tumour necrosis factor-alpha (TNF-alpha) in mouse peritoneal macrophages.

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    • "Three strains were cultured according to the previous report (Namba et al., 2010). After the centrifugation for 50 min at 12,000 × g at 4 • C, Triton X (TX)-114 (Wako) phase partitioning was performed to obtain MRF (Shimizu et al., 2008), and the pelleted MRF fraction was suspended in dimethyl sulfoxide (DMSO). The protein concentration was measured with a Micro BCA Protein Assay Kit (Thermo Scientific). "
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    ABSTRACT: Ureaplasma spp. are members of the family Mycoplasmataceae and have been considered to be associated with chorioamnionitis and preterm delivery. However, it is unclear whether Ureaplasma spp. have virulence factors related to these manifestations. The purpose of the present study was to determine whether the immunogenic protein multiple-banded antigen (MBA) from Ureaplasma parvum is a virulence factor for preterm delivery. We partially purified MBA from a type strain and clinical isolates of U. parvum, and also synthesized a diacylated lipopeptide derived from U. parvum, UPM-1. Using luciferase assays, both MBA-rich fraction MRF and UPM-1 activated the NF-κB pathway via TLR2. UPM-1 upregulated IL-1β, IL-6, IL-12p35, TNF-α, MIP2, LIX, and iNOS in mouse peritoneal macrophage. MRF or UPM-1 was injected into uteri on day 15 of gestation on pregnant C3H/HeN mice. The intrauterine MRF injection group had a significantly higher incidence of intrauterine fetal death (IUFD; 38.5%) than the control group (14.0%). Interestingly, intrauterine injection of UPM-1 caused preterm deliveries at high concentration (80.0%). In contrast, a low concentration of UPM-1 induced a significantly higher rate of fetal deaths (55.2%) than the control group (14.0%). The placentas of the UPM-1 injection group showed neutrophil infiltration and increased iNOS protein expression. Our data indicate that MBA from the clinical isolate of U. parvum is a potential virulence factor for IUFD and preterm delivery in mice and that the N-terminal diacylated lipopeptide is essential for the initiation of inflammation.
    Journal of Reproductive Immunology 10/2013; 100(2). DOI:10.1016/j.jri.2013.10.001 · 2.37 Impact Factor
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    • "Therefore, we wondered if activation of TLR 4 may also be a aspect in this disease. An important feature of Ureaplasma parvum is that this pathogen does not activate TLR 4, but does activate TLRs 1, 2, and 6 in macrophages (Shimizu et al., 2008). Moreover, ureaplasmas do not induce pro-inflammatory cytokine expression in uroepithelium as shown in Figure 1. "
    Clinical Management of Complicated Urinary Tract Infection, 09/2011; , ISBN: 978-953-307-393-4
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    • "As another common mycoplasma that causes diseases in human, Ureaplasma parvum has been examined to have several lipoproteins, such as P75 and P55 containing UU012 and UU016, respectively. They were found to activate NF-κB through TLR1, TLR2, and TLR6, and to induce tumor necrosis factor-α (TNF-α) production in mouse peritoneal macrophages (Shimizu et al., 2008b). All of these lipoproteins serve as potent cytokine inducers for monocytes/macrophages and have cytolytic activity. "
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    ABSTRACT: Mycoplasmas, the smallest free-living, self-replicating bacteria with diameters of 200 to 800 nm, have been reported to be associated with human diseases. It is well known that the mycoplasma lipoprotein/peptide is able to modulate the host immune system, whose N-terminal structure is an important factor in inducing immunity and distinguishing Toll-like receptors (TLRs). However, there is still no clear elucidation about the pathogenic mechanism of mycoplasma lipoprotein/peptide and the signaling pathway. Some researchers have focused on understanding the structures of these proteins and the relationships between their structure and biological function. This review provides an update on the research in this field.
    Journal of Zhejiang University SCIENCE B 01/2009; 10(1):67-76. DOI:10.1631/jzus.B0820256 · 1.29 Impact Factor
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