Pathogens and disease最新文献

Chlamydia trachomatis, C. pneumoniae, and C. psittaci, the three Chlamydia species known to cause human disease, have been collectively linked to several pathologies, including conjunctivitis, trachoma, respiratory disease, acute and chronic urogenital infections and their complications, and psittacosis. In vitro, animal, and human studies also established additional correlations, such as between C. pneumoniae and atherosclerosis and between C. trachomatis and ovarian cancer. As part of their survival and pathogenesis strategies as obligate intracellular bacteria, Chlamydia spp. modulate all three major types of epigenetic changes, which include deoxyribonucleic acid (DNA) methylation, histone post-translational modifications, and microRNA-mediated gene silencing. Some of these epigenetic changes may be implicated in key aspects of pathogenesis, such as the ability of the Chlamydia spp. to induce epithelial-to-mesenchymal transition, interfere with DNA damage repair, suppress cholesterol efflux from infected macrophages, act as a co-factor in human papillomavirus (HPV)-mediated cervical cancer, prevent apoptosis, and preserve the integrity of mitochondrial networks in infected host cells. A better understanding of the individual and collective contribution of epigenetic changes to pathogenesis will enhance our knowledge about the biology of Chlamydia spp. and facilitate the development of novel therapies and biomarkers. Pathogenic Chlamydia spp. contribute to epigenetically-mediated gene expression changes in host cells by multiple mechanisms.

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infections in humans. An association between persistent C. pneumoniae infection and asthma pathogenesis has been described. It is unknown whether specific immunoglobulin E (IgE) is a marker of persistent immune activation responses. Therefore, the association between C. pneumoniae-specific-IgE antibodies (Abs) and interferon (IFN)-gamma produced by C. pneumoniae-stimulated peripheral blood mononuclear cells (PBMC) was examined. Blood was collected and serum separated. PBMC from 63 children with or without stable asthma (N = 45 and 18, respectively) were infected or not infected with C. pneumoniae AR-39 and cultured for up to 7 days. Supernatants were collected, and IFN-gamma levels measured (ELISA). Serum C. pneumoniae-IgE Abs were detected by immunoblotting. C. pneumoniae-IgE Abs were detected in asthmatics (27%), compared with non-asthmatics (11%) (P = NS). IFN-gamma responses were more prevalent among asthmatics who had positive C. pneumoniae-IgE Abs (60%) compared with asthmatics without C. pneumoniae-IgE Abs (20%) (P = 0.1432). IFN-gamma responses in C. pneumoniae-stimulated PBMC from children with asthma were more frequent in children who had specific anti-C. pneumoniae-IgE Abs compared to those who did not. This immune response may reflect persistent infection, which may contribute to ongoing asthma symptoms.

Because the placenta is bathed in maternal blood, it is exposed to infectious agents and chemicals that may be present in the mother's circulation. Such exposures, which do not necessarily equate with transmission to the fetus, may primarily cause placental injury, thereby impairing placental function. Recent research has improved our understanding of the mechanisms by which some infectious agents are transmitted to the fetus, as well as the mechanisms underlying their impact on fetal outcomes. However, less is known about the impact of placental infection on placental structure and function, or the mechanisms underlying infection-driven placental pathogenesis. Moreover, recent studies indicate that noninfectious environmental agents accumulate in the placenta, but their impacts on placental function and fetal outcomes are unknown. Critically, diagnosing placental insults during pregnancy is very difficult and currently, this is possible only through postpartum placental examination. Here, with emphasis on humans, we discuss what is known about the impact of infectious and chemical agents on placental physiology and function, particularly in the absence of maternal-fetal transmission, and highlight knowledge gaps with potential implications for diagnosis and intervention against placental pathologies.

Murine herpesvirus 68 (MHV-68) belongs to the subfamily Gammaherpesvirinae of the family Herpesviridae. This exceptional murine herpesvirus is an excellent model for the study of human gammaherpesvirus infections. Cells infected with MHV-68 under nonpermissive conditions for viral replication produce substances designated as MHV-68 growth factors (MHGF-68), that can cause transformation of the cells, or on the other side, turn transformed cells into normal. It was already proposed, that the MHGF-68 fractions cause transformation, disruption of the cytoskeleton and slower growth of the tumors in nude mice. Here, we examined newly extracted fractions of MHGF-68 designated as F5 and F8. Both fractions proved to inhibit the growth of the spheroids and also tumours induced in nude mice. What more, the fractions caused the decrease of the protein levels of wt p53 and HIF-1α. Decreased levels of p53 and HIF-1α activity leads to decreased vascularization, slower tumour growth, and lower adaptation to hypoxic conditions. This would propose MHGF-68 fractions, or their human herpesvirus equivalents, as a potential anticancer drugs in combined chemotherapy.

The aim of the current study was to determine the activity of the delta-aminolevulinate dehydratase (δ-ALA-D) enzyme, oxidative stress biomarkers and the expression of cytokines in those infected with influenza B virus (IBV). To evaluate the activity of the δ-ALA-D enzyme, lipid peroxidation was estimated as levels of thiobarbituric acid reactive substances, protein and non-protein thiol groups, ferric-reducing antioxidant power (FRAP), vitamin C concentration and cytokine levels in IBV-infected individuals (n  = 50) and a control group (n = 30). δ-ALA-D activity was significantly lower in IBV-infected individuals compared with controls, as well as levels of thiols, vitamin C and FRAP. Lipid peroxidation and cytokine levels of IL-6, IL-10, IL-17A and IFN-y were statistically higher in the IBV group. In conclusion, we found evidence of the generation of oxidants, the depletion of the antioxidant system, decrease in the activity of the δ-ALA-D enzyme and an increase in the synthesis of cytokines, thus contributing to a better understanding of oxidative and inflammatory pathways during IBV infection.

Bacterial vaginosis, a type of vaginal inflammation, can be considered the main reason for abnormal discharges of the vagina and vaginal dysbiosis during reproductive years. Epidemiological investigations of females suffering from vaginitis demonstrated that at least 30% to 50% of all women had Bacterial vaginosis (BV). One of the fields of treatment is the use of probiotics, probiotics are commonly defined as viable microorganisms (yeasts or bacteria) that can positively affect the health of their hosts. They are used in foods, notably fermented milk products, and medicine-related products. The development of new probiotic strains is aimed at more active advantageous organisms. Lactobacillus species are the dominant bacteria in a normal vagina that can decrease the pH of the vagina by the production of lactic acid. A number of lactobacilli types can produce hydrogen peroxide as well. The presence of hydrogen peroxide-induced low pH can prevent the growth of several other microorganisms. The vaginal flora of BV cases can modify by replacing the Lactobacillus species with a high density of anaerobic bacteria (i.e. Mobiluncus sp. Bacteroides sp.), Mycoplasma hominis, and Gardnerella vaginalis. More vaginal infections are treated with medications, while there is a possibility of recurrence and chronic infection because of the adverse effects on the indigenous lactobacilli. Probiotics and prebiotics have shown capacities for optimizing, maintaining, and restoring the vaginal microflora. Therefore, biotherapeutics can offer alternative approaches to reduce infections of the vagina and thus promote consumers' health.

Burkholderia contaminans, a species of the Burkholderia cepacia complex-prevalent in certain Latin-American and European countries-can cause chronic pulmonary infection in persons with cystic fibrosis. Our aim was to gain insights into long-term lung infections with a focus on correlating how bacterial phenotypic traits in the chronic infection impact on patients' clinical outcome. Genotypic characteristics of 85 B. contaminans isolates recovered from 70 patients were investigated. For 16 of those patients, the clinical status and bacterial phenotypic characteristics, e.g. several virulence factors, phenotypic variants, and the antimicrobial susceptibility pattern, were evaluated. Two clones were found in the whole bacterial population: (i) the multiresistant ST 872 PCR-recA-RFLP-HaeIII-K-pattern clone, which carries a pathogenic island homologous to BcenGI11 of B. cenocepacia J2315, and (ii) the ST 102 PCR-recA-RFLP-HaeIII-AT-pattern clone. The emergence of certain bacterial phenotypes in the chronic infection such as the nonmucoid phenotype, small colony variants, brownish pigmented colonies, and hypermutators, proved to be, together with coinfection with Pseudomonas aeruginosa, the possible markers of more challenging infections and poor prognosis. The presence of cocolonizers and the bacterial phenotypes that are especially adapted to persist in long-term respiratory tract infections have a crucial role in patients' clinical outcomes.

The coronavirus disease (COVID-19) pandemic has imposed deployment of an effective vaccine as a worldwide health priority. The new variants of SARS-CoV-2 have also brought serious concerns due to virus eradiation hesitancy. In this study, we evaluated the protective immune system activity of a recombinant viral vector-based vaccine candidate encoding a fusion spike, membrane and nucleocapsid proteins, Spike (528-1273aa)-M-N, in BALB/c via two different routes of delivery, intranasal and subcutaneous. The immune responses were then assessed through specific SARS-CoV-2 antibodies, interleukin and granzyme B secretion. The outcomes showed that the IgG titer and IgA secretion was higher in intranasal route in comparison with the subcutaneous, and what is more, a higher titer of IL-4 was detected through the intranasal route, whereas IFN-γ was highly induced via the subcutaneous route. The cytotoxic cell activities were mostly achieved via subcutaneous route immunization. Vaccination with the target antigen is immunogenic and led to induction of specific antibodies. Both humoral and cellular immunity arms were well activated in immunized mice, especially through intranasal route with detectable IgA and IgG. Therefore, implication of the platform as a potential vaccine candidate has potential as a future prophylactic vaccine that guarantees further investigations for the assessment of its immunogenicity in humans.

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon.

Hypoxia-inducible factor (HIF)1α is a transcription factor involved in cellular metabolism and regulation of immune cell effector functions. Here, we studied the role of HIF1α in myeloid cells during pneumonia caused by the major causative pathogen, Streptococcus pneumoniae (Spneu). Mice deficient for HIF1α in myeloid cells (LysMcreHif1αfl/fl) were generated to study the in vitro responsiveness of bone marrow-derived macrophages (BMDMs) and alveolar macrophages (AMs) to the Gram-positive bacterial wall component lipoteichoic acid (LTA) and heat-killed Spneu, and the in vivo host response after infection with Spneu via the airways. Both BMDMs and AMs released more lactate upon stimulation with LTA or Spneu, indicative of enhanced glycolysis; HIF1α-deficiency in these cells was associated with diminished lactate release. In BMDMs, HIF1α-deficiency resulted in reduced secretion of tumor necrosis factor (TNF)α and interleukin (IL)-6 upon activation with Spneu but not LTA, while HIF1α-deficient AMs secreted less TNFα and IL-6 in response to LTA, and TNFα after Spneu stimulation. However, no difference was found in the host response of LysMcreHif1αfl/fl mice after Spneu infection as compared to controls. Similar in vivo findings were obtained in neutrophil (Mrp8creHif1αfl/fl) HIF1α-deficient mice. These data suggest that myeloid HIF1α is dispensable for the host defense during pneumococcal pneumonia.