DnaJ, a promising vaccine candidate against Ureaplasma urealyticum infection.

Ureaplasma urealyticum (U. urealyticum, Uu) is a common sexually transmitted pathogen that is responsible for diseases such as non-gonococcal urethritis, chorioamnionitis, and neonatal respiratory diseases. The rapid emergence of multidrug-resistant bacteria threatens the effective treatment of Uu infections. Considering this, vaccination could be an efficacious medical intervention to prevent Uu infection and disease. As a highly conserved molecular chaperone, DnaJ is expressed and upregulated by pathogens soon after infection. Here, we assessed the vaccine potential of recombinant Uu-DnaJ in a mouse model and dendritic cells. Results showed that intramuscular administration of DnaJ induced robust humoral- and T helper (Th) 1 cell-mediated immune responses and protected against genital tract infection, inflammation, and the pathologic sequelae after Uu infection. Importantly, the DnaJ protein also induced the maturation of mouse bone marrow-derived dendritic cells (BMDCs), ultimately promoting naïve T cell differentiation toward the Th1 phenotype. In addition, adoptive immunization of DnaJ-pulsed BMDCs elicited antigen-specific Immunoglobulin G2 (IgG2) antibodies as well as a Th1-biased cellular response in mice. These results support DnaJ as a promising vaccine candidate to control Uu infections. KEY POINTS: • A novel recombinant vaccine was constructed against U. urealyticum infection. • Antigen-specific humoral and cellular immune responses after DnaJ vaccination. • Dendritic cells are activated by Uu-DnaJ, which results in a Th1-biased immune response.

[Advances in immune escape mechanism of Ureaplasma species: Review].

Ureaplasma urealyticum and Ureaplasma parvum are the most common Ureaplasma species causing repeated or persistent infection of the urogenital tract. The host can mobilize innate and adaptive immunity to defend and eliminate pathogens. However, under certain conditions, the host's immune protection cannot completely clear Ureaplasma species. Ureaplasma species have evolved a complex and sophisticated escape mechanism in the long-term defense against host immune protection. This article summarizes the research progress on Ureaplasma species' immune escape mechanism from several aspects such as evading host autophagy mechanism, antagonizing host nutritional immunity and regulating host cell gene expression.

GrpE Immunization Protects Against Ureaplasma urealyticum Infection in BALB/C Mice.

Nucleotide exchange factor (GrpE), a highly conserved antigen, is rapidly expressed and upregulated when Ureaplasma urealyticum infects a host, which could act as a candidative vaccine if it can induce an anti-U. urealyticum immune reaction. Here, we evaluated the vaccine potential of recombinant GrpE protein adjuvanted by Freund's adjuvant (FA), to protect against U. urealyticum genital tract infection in a mouse model. After booster immunization in mice with FA, the GrpE can induced both humoral and cellular immune response after intramuscular injection into BALB/c mice. A strong humoral immune response was detected in the GrpE-immunized mice characterized by production of high titers of antigen-specific serum IgG (IgG1, IgG2a, and IgG3) antibodies. At the same time, the GrpE also induced a Th1-biased cytokine spectrum with high levels of IFN-γ and TNF-α after re-stimulation with immunogen GrpE in vitro, suggesting that GrpE could trigger the Th1 response when used for vaccination in the presence of FA. Although GrpE vaccination in the presence of a Th1-type adjuvant-induced had readily detectable Th1 responses, there wasn't increase inflammation in response to the infection. More importantly, the robust immune responses in mice after immunization with GrpE showed a significantly reduced U. urealyticum burden in cervical tissues. Histopathological analysis confirmed that tissues of GrpE-immunized BALB/c mice were protected against the pathological effects of U. urealyticum infection. In conclusion, this study preliminarily reveals GrpE protein as a promising new candidate vaccine for preventing U. urealyticum reproductive tract infection.

Hypothetical protein Cpn0423 triggers NOD2 activation and contributes to Chlamydia pneumoniae-mediated inflammation.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is pathogenic to humans, by causing pulmonary inflammation or bronchitis in both adolescents and young adults. However, the molecular signals linking C. pneumoniae components to inflammation remain elusive. This study was to investigate the effect of Chlamydia-specific Cpn0423 of C. pneumoniae on C. pneumoniae-mediated inflammation. RESULTS: Cpn0423 was detected outside of C. pneumoniae inclusions, which induced production of several cytokines including macrophage inflammatory protein-2 (MIP-2) and interleukins (ILs). Production of the Cpn0423-induced cytokines was markedly reduced in cells pretreated with NOD2-siRNA, but not with negative control oligonucleotides. Mice treated with Cpn0423 through intranasal administration exhibited pulmonary inflammation as evidenced by infiltration of inflammatory cells, increased inflammatory scores in the lung histology, recruitment of neutrophils and increased cytokines levels in the BALF. CONCLUSION: Cpn0423 could be sensed by NOD2, which was identified as an essential element in a pathway contributing to the development of C. pneumoniae -mediated inflammation.

Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population.

BACKGROUND AND AIM: Hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are known to be prevalent in injection drug users (IDUs); however, the relationship between the molecular epidemiologic features of hepatitis virus infection in high-risk individuals and the general population has not yet been established. METHODS: In total, 1049 IDUs and 672 individuals who underwent physical examinations at Chenzhou hospital, Hunan Province, China, were enrolled. HBV, HCV, and HDV infections were screened with serologic tests in both populations. HBsAg-positive, anti-HCV IgG-positive, and anti-HDV IgG-positive samples were further confirmed by polymerase chain reaction, quantitative polymerase chain reaction, and DNA sequencing. RESULTS: Significantly higher HBV (21.54 vs 16.52%, P = 0.01), HCV (45.95% vs 1.34%, P < 0.001), and HDV (5.62% vs 0.30%, P < 0.001) infections were detected in IDUs compared with the general population. The dual infection of HBV/HCV or HBV/HDV was also significantly higher in IDUs than in the general population. HBV genotype B and HDV genotype II were dominants in both populations. HCV infection showed genotype 6a (49.52%) dominant in IDUs, but genotype 1b accounted for 50% infection, which was followed by genotype 6a (33.33%) in the general population. Higher viral loads were associated with HBV genotype B and HCV genotype 6a compared with non-dominant genotypic infections. CONCLUSIONS: HBV and HDV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations. Our results suggest different molecular epidemiologic characteristics of HBV, HCV, and HDV infection in two populations.

A ferritin-like protein with antioxidant activity in Ureaplasma urealyticum.

BACKGROUND: Ureaplasma urealyticum is a major pathogen associated with many diseases. The ability of U. urealyticum to protect itself from oxidative stress is likely to be important for its pathogenesis and survival, but its oxidative stress tolerance mechanisms remain unclear. This study investigates the antioxidant activity of a ferritin-like protein from U. urealyticum. RESULTS: The uuferritin gene, which was up regulated when U. urealyticum was subjected to oxidative stress, was cloned from U. urealyticum and the corresponding recombinant protein uuferritin was purified. Uuferritin protein reduced the levels of hydroxyl radicals generated by the Fenton reaction as a consequence of its ferroxidase activity, and thus the protein protected DNA from oxidative damage. Furthermore, oxidation-sensitive Escherichia coli mutants transformed with pTrc99a-uuferritin showed significantly improved tolerance to oxidative stress compared to E. coli mutants transformed with an empty pTrc99a vector. CONCLUSIONS: The present work shows that uuferritin protein confers resistance to oxidative stress in vitro and in E. coli. The protective role of uuferritin provides a foundation for understanding the mechanisms of oxidative stress tolerance in U. urealyticum.