Pathogens and disease最新文献

{"title":"Leprosy reactions: Unraveling immunological mechanisms underlying tissue damage in leprosy patients.","authors":"Héctor Serrano-Coll, Eric L Wan, Lina Restrepo-Rivera, Nora Cardona-Castro","doi":"10.1093/femspd/ftae013","DOIUrl":"10.1093/femspd/ftae013","url":null,"abstract":"<p><p>Leprosy is a chronic granulomatous infectious and disabling disease caused by two mycobacteria, Mycobacterium leprae and Mycobacterium lepromatosis. Acute inflammatory responses, known as leprosy reactions, are significant contributors to disabilities. Three types of leprosy reactions have been identified based on excessive cytokine release (e.g. type 1) or the accumulation of immune complexes in tissues inducing multiorgan damage (e.g. types 2 and 3). The type of leprosy reaction has implications on treatment and management strategies, yet are not well understood by health workers caring for leprosy patients. We attempt to describe the immunologic mechanisms behind the different leprosy reactions and the rationale for tailoring clinical treatment and management to the particular type of leprosy reaction based on the underlying immunologic situation.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A suitable and efficient optimization system for the culture of Chlamydia trachomatis in adult inclusion conjunctivitis.","authors":"Yuan Wei, Xizhan Xu, Leying Wang, Qiankun Chen, Jinsong Li, Xiafei Liu, Zhenyu Wei, Jinding Pang, Yan Peng, Xiaoyan Guo, Zhen Cheng, Zhiqun Wang, Yang Zhang, Kexin Chen, Xinxin Lu, Qingfeng Liang","doi":"10.1093/femspd/ftae020","DOIUrl":"10.1093/femspd/ftae020","url":null,"abstract":"<p><p>The prevalence of Chlamydia trachomatis infection in the genitourinary tract is increasing, with an annual rise of 9 million cases. Individuals afflicted with these infections are at a heightened risk of developing adult inclusive conjunctivitis (AIC), which is commonly recognized as the ocular manifestation of this sexually transmitted infection. Despite its significant clinical implications, the lack of distinctive symptoms and the overlap with other ocular conditions often lead to underdiagnosis or misdiagnosis of AIC associated with C. trachomatis infection. Here, we established six distinct C. trachomatis culture cell lines, specifically highlighting the MA104 N*V cell line that exhibited diminished expression of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1), resulting in reduced interferons. Infected MA104 N*V cells displayed the highest count of intracytoplasmic inclusions detected through immunofluorescence staining, peaking at 48 h postinfection. Subsequently, MA104 N*V cells were employed for clinical screening in adult patients diagnosed with AIC. Among the evaluated cohort of 20 patients, quantitative PCR (qPCR) testing revealed positive results in seven individuals, indicating the presence of C. trachomatis infection. Furthermore, the MA104 N*V cell cultures derived from these infected patients demonstrated successful cultivation and replication of the pathogen, confirming its viability and infectivity. Molecular genotyping identified four distinct urogenital serovars, with serovar D being the most prevalent (4/7), followed by E (1/7), F (1/7), and Ia (1/7). This novel cellular model contributes to studies on C. trachomatis pathogenesis, molecular mechanisms, and host-pathogen interactions both in vitro and in vivo. It also aids in acquiring clinically relevant strains critical for advancing diagnostics, treatments, and vaccines against C. trachomatis.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of prime-boost strategies on the protective efficacy and immunogenicity of a PLGA (85:15)-encapsulated Chlamydia recombinant MOMP nanovaccine.","authors":"Rajnish Sahu, Richa Verma, Timothy E Egbo, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis","doi":"10.1093/femspd/ftae004","DOIUrl":"10.1093/femspd/ftae004","url":null,"abstract":"<p><p>To begin to optimize the immunization routes for our reported PLGA-rMOMP nanovaccine [PLGA-encapsulated Chlamydia muridarum (Cm) recombinant major outer membrane protein (rMOMP)], we compared two prime-boost immunization strategies [subcutaneous (SC) and intramuscular (IM-p) prime routes followed by two SC-boosts)] to evaluate the nanovaccine-induced protective efficacy and immunogenicity in female BALB/c mice. Our results showed that mice immunized via the SC and IM-p routes were protected against a Cm genital challenge by a reduction in bacterial burden and with fewer bacteria in the SC mice. Protection of mice correlated with rMOMP-specific Th1 (IL-2 and IFN-γ) and not Th2 (IL-4, IL-9, and IL-13) cytokines, and CD4+ memory (CD44highCD62Lhigh) T-cells, especially in the SC mice. We also observed higher levels of IL-1α, IL-6, IL-17, CCL-2, and G-CSF in SC-immunized mice. Notably, an increase of cytokines/chemokines was seen after the challenge in the SC, IM-p, and control mice (rMOMP and PBS), suggesting a Cm stimulation. In parallel, rMOMP-specific Th1 (IgG2a and IgG2b) and Th2 (IgG1) serum, mucosal, serum avidity, and neutralizing antibodies were more elevated in SC than in IM-p mice. Overall, the homologous SC prime-boost immunization of mice induced enhanced cellular and antibody responses with better protection against a genital challenge compared to the heterologous IM-p.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of beta2-adrenergic receptor knockout mouse model during Chlamydia muridarum genital infection.","authors":"Tesfaye Belay, Rajnish Sahu, Vida Dennis, Kaitlyn Cook, Alexis Ray, Danielle Baker, Ashlei Kelly, Nathasha Woart","doi":"10.1093/femspd/ftae029","DOIUrl":"10.1093/femspd/ftae029","url":null,"abstract":"<p><p>Chlamydia genital infection caused by Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. A mouse model has been developed in our laboratory to better understand the effect of cold-induced stress on chlamydia genital infection and immune response. However, the stress mechanism affecting the host response to Chlamydia muridarum genital infection remains unclear. Here, we demonstrate a role for the beta2-adrenergic receptor (β2-AR), which binds noradrenaline and modulates the immune response against chlamydia genital infection in a mouse model. A successful β2-AR homozygous knockout (KO) mouse model was used to study the infection and analyze the immune response. Our data show that stressed mice lacking the β2-AR are less susceptible to C. muridarum genital infection than controls. A correlation was obtained between lower organ load and higher interferon-gamma production by CD4+ and CD8+ cells of the KO mice. Furthermore, exposure of CD4+ T cells to noradrenaline alters the production of cytokines in mice during C. muridarum genital infection. This study suggests that the blockade of β2-AR signaling could be used to increase resistance to chlamydia genital infection. We value the β2-AR KO as a viable model that can provide reproducible results in investigating medical research, including chlamydia genital infection.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coxiella burnetii protein CBU2016 supports CCV expansion.","authors":"David R Thomas, Sarah E Garnish, Chen Ai Khoo, Bhavna Padmanabhan, Nichollas E Scott, Hayley J Newton","doi":"10.1093/femspd/ftae018","DOIUrl":"10.1093/femspd/ftae018","url":null,"abstract":"<p><p>Coxiella burnetii is a globally distributed obligate intracellular pathogen. Although often asymptomatic, infections can cause acute Q fever with influenza-like symptoms and/or severe chronic Q fever. Coxiella burnetii develops a unique replicative niche within host cells called the Coxiella-containing vacuole (CCV), facilitated by the Dot/Icm type IV secretion system translocating a cohort of bacterial effector proteins into the host. The role of some effectors has been elucidated; however, the actions of the majority remain enigmatic and the list of true effectors is disputable. This study examined CBU2016, a unique C. burnetii protein previously designated as an effector with a role in infection. We were unable to validate CBU2016 as a translocated effector protein. Employing targeted knock-out and complemented strains, we found that the loss of CBU2016 did not cause a replication defect within Hela, THP-1, J774, or iBMDM cells or in axenic media, nor did it affect the pathogenicity of C. burnetii in the Galleria mellonella infection model. The absence of CBU2016 did, however, result in a consistent decrease in the size of CCVs in HeLa cells. These results suggest that although CBU2016 may not be a Dot/Icm effector, it is still able to influence the host environment during infection.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restriction and evasion: a review of IFNγ-mediated cell-autonomous defense pathways during genital Chlamydia infection.","authors":"Jeffrey R Reitano, Jörn Coers","doi":"10.1093/femspd/ftae019","DOIUrl":"10.1093/femspd/ftae019","url":null,"abstract":"<p><p>Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection (STI) in the USA. As an STI, C. trachomatis infections can cause inflammatory damage to the female reproductive tract and downstream sequelae including infertility. No vaccine currently exists to C. trachomatis, which evades sterilizing immune responses in its human host. A better understanding of this evasion will greatly benefit the production of anti-Chlamydia therapeutics and vaccination strategies. This minireview will discuss a single branch of the immune system, which activates in response to genital Chlamydia infection: so-called \"cell-autonomous immunity\" activated by the cytokine interferon-gamma. We will also discuss the mechanisms by which human and mouse-adapted Chlamydia species evade cell-autonomous immune responses in their native hosts. This minireview will examine five pathways of host defense and their evasion: (i) depletion of tryptophan and other nutrients, (ii) immunity-related GTPase-mediated defense, (iii) production of nitric oxide, (iv) IFNγ-induced cell death, and (v) RNF213-mediated destruction of inclusions.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11407441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential patterns of antibody response against SARS-CoV-2 nucleocapsid epitopes detected in sera from patients in the acute phase of COVID-19, convalescents, and pre-pandemic individuals.","authors":"Agnieszka Razim, Katarzyna Pacyga-Prus, Wioletta Kazana-Płuszka, Agnieszka Zabłocka, Józefa Macała, Hubert Ciepłucha, Andrzej Gamian, Sabina Górska","doi":"10.1093/femspd/ftae025","DOIUrl":"10.1093/femspd/ftae025","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already infected more than 0.7 billion people and caused over 7 million deaths worldwide. At the same time, our knowledge about this virus is still incipient. In some cases, there is pre-pandemic immunity; however, its source is unknown. The analysis of patients' humoral responses might shed light on this puzzle. In this paper, we evaluated the antibody recognition of nucleocapsid protein, one of the structural proteins of SARS-CoV-2. For this purpose, we used pre-pandemic acute COVID-19 and convalescent patients' sera to identify and map nucleocapsid protein epitopes. We identified a common epitope KKSAAEASKKPRQKRTATKA recognized by sera antibodies from all three groups. Some motifs of this sequence are widespread among various coronaviruses, plants or human proteins indicating that there might be more sources of nucleocapsid-reactive antibodies than previous infections with seasonal coronavirus. The two sequences MSDNGPQNQRNAPRITFGGP and KADETQALPQRQKKQQTVTL were detected as specific for sera from patients in the acute phase of infection and convalescents making them suitable for future development of vaccines against SARS-CoV-2. Knowledge of the humoral response to SARS-CoV-2 infection is essential for the design of appropriate diagnostic tools and vaccine antigens.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of bacteriophage vB_AbaS_SA1 and its synergistic effects with antibiotics against clinical multidrug-resistant Acinetobacter baumannii isolates.","authors":"Sanaz Rastegar, Salehe Sabouri, Omid Tadjrobehkar, Ali Samareh, Hira Niaz, Nafise Sanjari, Hossein Hosseini-Nave, Mikael Skurnik","doi":"10.1093/femspd/ftae028","DOIUrl":"10.1093/femspd/ftae028","url":null,"abstract":"<p><p>Acinetobacter baumannii is a major cause of nosocomial infections globally. The increasing prevalence of multidrug-resistant (MDR) A. baumannii has become an important public health concern. To combat drug resistance, alternative methods such as phage therapy have been suggested. In total, 30 MDR A. baumannii strains were isolated from clinical specimens, and their antibiotic susceptibilities were determined. The Acinetobacter phage vB_AbaS_SA1, isolated from hospital sewage, was characterized. In addition to its plaque size, particle morphology, and host range, its genome sequence was determined and annotated. Finally, the antibacterial effects of phage alone, antibiotics alone, and phage/antibiotic combinations were assessed against the A. baumannii strains. Phage vB_AbaS_SA1 had siphovirus morphology, showed a latent period of 20 min, and a 250 PFU/cell (plaque forming unit/cell) burst size. When combined with antibiotics, vB_AbaS_SA1 (SA1) showed a significant phage-antibiotic synergy effect and reduced the overall effective concentration of antibiotics in time-kill assessments. The genome of SA1 is a linear double-stranded DNA of 50 108 bp in size with a guanine-cytosine (GC) content of 39.15%. Despite the potent antibacterial effect of SA1, it is necessary to perform additional research to completely elucidate the mechanisms of action and potential constraints associated with utilizing this bacteriophage.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of human respiratory pathogens and associated mucosal cytokine levels in young children and adults: a cross-sectional observational study in the Netherlands during the winter of 2012/2013.","authors":"Puck B van Kasteren, Anne T Gelderloos, Mioara Alina Nicolaie, Gerco den Hartog, Marloes Vissers, Willem Luytjes, Nynke Y Rots, Josine van Beek","doi":"10.1093/femspd/ftae010","DOIUrl":"10.1093/femspd/ftae010","url":null,"abstract":"<p><p>Respiratory pathogens can cause severe disease and even death, especially in the very young and very old. Studies investigating their prevalence often focus on individuals presenting to healthcare providers with symptoms. However, the design of prevention strategies, e.g. which target groups to vaccinate, will benefit from knowledge on the prevalence of, risk factors for and host response to these pathogens in the general population. In this study, upper respiratory samples (n = 1311) were collected cross-sectionally during winter from 11- and 24-month old children, their parents, and adults ≥60 years of age that were recruited irrespective of seeking medical care. Almost all children, approximately two-thirds of parents and a quarter of older adults tested positive for at least one pathogen, often in the absence of symptoms. Viral interference was evident for the combination of rhinovirus and respiratory syncytial virus. Attending childcare facilities and having siblings associated with increased pathogen counts in children. On average, children showed increased levels of mucosal cytokines compared to parents and especially proinflammatory molecules associated with the presence of symptoms. These findings may guide further research into transmission patterns of respiratory pathogens and assist in determining the most appropriate strategies for the prediction and prevention of disease.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-edited duck enteritis virus expressing Pmp17G of Chlamydia psittaci induced protective immunity in ducklings.","authors":"Jiaqi Liu, Yihui Wang, Na Tang, Cheng He, Fuhuang Li","doi":"10.1093/femspd/ftae027","DOIUrl":"10.1093/femspd/ftae027","url":null,"abstract":"<p><p>Chlamydia psittaci is threatening to the animal industry and human beings. Live attenuated duck enteritis virus (DEV) is considered a good vaccine vector. In the present study, the Pmp17G antigen of C. psittaci was expressed in DEV to construct a recombinant DEV-Pmp17G vaccine. The growing curve of the rDEV-Pmp17G vaccine was comparable to the parental DEV strain, and Pmp17G protein expression was detected in the cytosol and membrane of the infected host cells. A total of 30 ducklings assigned to 5 groups were used to evaluate the vaccine efficacy. The birds in the vaccine groups received 15 000 plaque forming units of the rDEV-Pmp17G vaccine via hypodermic injection. In contrast, the control groups received intramuscular inoculation with 1 × 103 embryo lethal dose of DEV vector or 50 µg of commercial recombinant major outer membrane protein (MOMP) vaccine. The rDEV-Pmp17G vaccine induced significantly higher levels of IgG antibodies than the commercial MOMP did on day 14, and the IgG antibodies persisted for 28 days. Moreover, the rDEV-Pmp17G vaccine also induced higher levels of lymphocyte proliferations compared to the DEV vector. The vaccinated animals significantly reduced lesions and enhanced bacterial clearance in the lungs and throats compared to the MOMP immunization. Thus, the rDEV-Pmp17G vaccine induced persistent IgG antibodies and lymphocyte proliferation against C. psittaci infection.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}