Journal of Microbiology Immunology and Infection最新文献

The proportion of trough plasma concentration of dolutegravir (DTG) above protein adjusted 90 % inhibition concentration (IC90) (0.064 mg/L) was 98.1 % across all visits during the twelve doses of once-weekly rifapentine and isoniazid (3HP) in people with HIV (PWH). Furthermore, the participants maintained a high rate of HIV viral suppression (98 %) within 6 months after completing 3HP.

Background: Neutrophils are vital constituents of the immune response in the vaginal environment, playing a pivotal role in the defense against trichomoniasis. Earlier studies have shown that Trichomonas vaginalis (T. vaginalis) can release leukotriene B4 (LTB4), a molecule that attracts and activates neutrophils. Additionally, secretory products from this parasite can induce the production of interleukin-8 (IL-8) in mast cells and neutrophils, which further recruits neutrophils to the infection site. The precise reasons behind T. vaginalis actively promoting interaction between parasites and neutrophils rather than inhibiting the inflammatory response remain unclear.

Results: In this study, we collected conditioned medium to elucidate the intricate dynamics between T. vaginalis and human neutrophils. We conducted a comprehensive profiling of soluble excretory/secretory proteins (ESPs), identifying 192 protein spots, of which 94 were successfully characterized through mass spectrometry analysis. Notably, the majority of induced ESPs from co-cultivation exhibited consistency with the trichomonad and neutrophil standalone groups, except for lactoferrin, which was observed exclusively following the interaction between neutrophils and T. vaginalis. The secretion of lactoferrin was determined to be a contact-dependent process. It was interesting to identify the ability of the iron-loaded lactoferrin to extend the survival time of T. vaginalis under iron-deficient conditions.

Conclusions: This study represents the first to identify the origin of lactoferrin during T. vaginalis infection, shedding light on the potential reason for T. vaginalis's ability to attract neutrophils to the infection site: the acquisition of the iron source, lactoferrin.

Background: Angiostrongylus cantonensis is a significant foodborne zoonotic parasite that causes severe neuropathological damage and symptoms in humans. Excretory-secretory products (ESPs) play a pivotal role in elucidating host-parasite interactions and can aid in penetrating host defensive barriers in helminths. Recently, secreted microRNAs have become important research targets for parasite-host communication. In this study, we determined the expression and function of novel microRNAs from A. cantonensis L5 ESPs and evaluated the effect of target microRNAs on the molecular mechanisms of mouse astrocytes.

Methods: Here, we employed next-generation sequencing (NGS) to establish the secreted microRNAs dataset. Next, we evaluated the effects of AcESPs-microRNAs in A. cantonensis ESPs treated astrocytes.

Results: First, we established the secreted microRNA dataset, and then comprehensively verified the characteristics. Novel microRNAs were initially detected, and their expression was found. Moreover, the prediction results showed that these secreted microRNAs may regulate Wnt and mTOR signaling. Next, the data showed that the AcNOVEL55 microRNA reduced cell apoptosis generation via regulating the RhoA-Rock signaling pathway in A. cantonensis L5 ESPs treated mouse astrocytes. Moreover, we also demonstrated that the AcNOVEL31 microRNA can affect the inflammation activation via regulating the presenilin-1/GSK3B/β-catenin/NF-κB pathway. Finally, the concentrations of secreted IL-6 and IL-12 proteins were downregulated by AcNOVEL31 microRNA by influencing presenilin-1 expression.

Conclusion: This is the first study to verify the molecular functions of novel microRNAs secreted by A. cantonensis. The discovery of the microRNA mechanisms by which cross-species parasitic nematodes influence hosts has advanced research on host-parasitic nematode interactions.

We review the epidemiology, policies, and control programs of HIV infection in Taiwan in the past 40 years since the first case of HIV infection was diagnosed in 1984. With the introduction of combination antiretroviral therapy (ART) in Taiwan in 1997, the incidences of HIV-related opportunistic illnesses and mortality have significantly declined. However, despite improved access to HIV testing and treatment, late presentation of HIV infection remains common. Unprotected sex, particularly among men who have sex with men, continues to be the leading risk for HIV transmission after implementation of harm reduction program to control an outbreak of HIV infection among people who inject drugs that occurred in 2003-2007. The sequential introduction of well-tolerated, effective, single-tablet antiretroviral regimens has facilitated the implementation of "treat-all" policy in 2016, rapid ART initiation within 7 days of diagnosis in 2018, and same-day ART initiation in 2021 when immunochromatography was used for rapid confirmation of HIV infection. Government-funded pilot program of pre-exposure prophylaxis for HIV infection, which was launched in 2016 followed by wider enrollment of people at high risk for HIV acquisition in 2018, have contributed to sustained declines of the incidence of HIV infection since 2018, along with high rates of linkage to HIV care, ART initiation, viral suppression, and retention in care in Taiwan. Challenges remain to achieve HIV elimination and long-term successful management of HIV infection, which include stigma and discrimination, late presentation of HIV infection, and accelerated ageing with increasing rates of co-morbidities among people with HIV.

Background/purpose(s): Dengue virus (DENV) is one of the most troublesome mosquito-borne infectious viruses in tropical and subtropical zones. People with secondary/multiple DENV infections are at an increased risk of developing severe dengue. Both monocytes and T cells are known to play important roles in the immune response against DENV. However, the function of monocytes and T cells in individuals with potentially multiple exposures to DENV is rarely reported.

Method: In the present study, we performed a functional analysis of monocytes and T cells from people with previous DENV infection and DENV-naïve people that stimulated with DENV2 ex vivo.

Results: Our preliminary analysis indicated that the response of monocytes and T cells to DENV2 restimulation was comparable between DENV-exposed and DENV-naïve individuals. Furthermore, the cytokine expression profiles in monocytes from both naïve individuals and previously DENV-exposed subjects were similar after DENV2 stimulation. In addition, it was observed that the function of T cells was also equivalent when monocytes were present as antigen-presenting cells for dengue antigen, NS3, in terms of cell proliferation, interferon-gamma (IFNγ) secretion, and memory response.

Conclusions: Based on the results, it was observed that previously DENV-exposed monocytes and T cells seemed to be anergic during DENV reinfection. However, whether the impaired response of monocytes and T cells against DENV in people with a history of previous DENV infection leads to severe dengue upon secondary infection in endemic areas requires further investigation.

Background: Cigarette smoking remains a leading cause of mortality worldwide. Streptococcus pneumoniae, also known as pneumococcus, is one of the most common pathogens that colonizes the human respiratory tract, causing life-threatening infections. Several studies have reported that cigarette smoke (CS) exposure promotes pneumococcal infectivity; however, the underlying mechanisms remain to be illustrated.

Methods: In this study, we prepared cigarette smoke extract (CSE) from tobacco containing nicotine (0.8 mg/cigarette) and tar (10 mg/cigarette) to investigate the effects of CSE on innate immune response using murine macrophage models.

Results: The results from the cytokine array showed that the production of C-C Motif Chemokine Ligand 2 (CCL2), CCL4, CCL3, C-X-C Motif Chemokine Ligand 2 (CXCL2), and CXCL-10, in pneumococcus-infected cells was reduced upon 5 % CSE treatment. Our results further demonstrated that 5 % CSE exposure, followed by pneumococcal challenge, significantly decreased CCL2 and type I interferon (IFN) production in macrophages by inhibiting nuclear factor (NF)-κB and IFN regulatory factor 3 (IRF3) signaling pathways. Moreover, CSE disrupts macrophage polarization and impedes innate immune signaling to suppress pneumococcal phagocytosis by macrophages.

Conclusion: Our results provide evidence that CS manipulates the signaling molecules to subvert macrophage functions, thereby hindering the innate response against pneumococcal infection.

Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucial. Acetyl-phosphate (AcP) is essential for bacterial metabolism and can affect virulence factor expression. However, the role of the Pta-AckA pathway, which regulates AcP levels, in K. pneumoniae pathogenesis remains unclear.

Methods: Deletion mutants lacking the pta and ackA, involved in AcP production and hydrolysis, were generated in K. pneumoniae CG43S3. Their effects on AcP levels, the patterns of global acetylated protein, capsular polysaccharide (CPS) amount, serum resistance, type 3 fimbriae expression, biofilm formation, and virulence in G. mellonella larva were assessed.

Results: Deletion of ackA in K. pneumoniae CG43S3 led to AcP accumulation, while pta deletion abolished AcP synthesis when grown in TB7+1 % glucose. This pathway influenced global protein acetylation, with pta deletion decreasing acetylation and ackA deletion increasing it. Additionally, pta deletion decreased the CPS amount, serum resistance, and type 3 fimbriae expression, while ackA deletion increased these factors. Furthermore, deleting pta and ackA attenuated the infected larva's virulence and death rate.

Conclusion: Our findings highlight the critical role of the Pta-AckA pathway in K. pneumoniae pathogenesis. This pathway regulates AcP levels, global protein acetylation, CPS production, serum resistance, and type 3 fimbriae expression, ultimately impacting virulence. The information provides insights into potential therapeutic targets for combating K. pneumoniae infection.

Background: The inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) is a complex disease with multifactorial etiology. The intestinal dysbiosis have been investigated to play an important role in IBD pathogenesis and disease activity. The aim of our study was to analyze the intestinal microbiota composition in IBD across different severity levels and the impact of biologic therapy on microbiota modulation.

Methods: In this study, 27 IBD patients were recruited, including 14 patients undergoing biologic therapy for moderate to severe disease activity and 13 controls with inactive disease. The gut microbial composition was determined by 16 S ribosomal RNA gene sequencing of stool samples.

Results: Biologic therapy led to significant clinical improvement in IBD disease activity after 48 weeks. About species richness, community alpha diversity was significant lower in active CD patients and enriched gradually after biologic therapy. The beta-diversity regard to the difference of bacterial community composition showed significant difference between patients in biologic and control group. A decrease in Firmicutes and increase in Bacteroidetes abundance were observed in patients with active disease, both in CD and UC. Biologic treatment induced shifts in gut microbiota, with increased Firmicutes and decreased Bacteroidetes, as well as improved F/B ratio gradually after treatment, correlating with disease activity.

Conclusions: Our study suggested that gut microbiota differences changed after biologic therapies among IBD with different disease activity, and a rising Firmicutes/Bacteroidetes ratio could be a potential predictor for disease activity and treatment response monitoring.

Background: Hemodialysis patients exhibit a reduced response to vaccination and have different vaccine dose regimens. Vaccines induce antibodies and affect the inflammatory balance through antibody glycosylation and effector functions. Therefore, we aimed to analyze the antibody glycosylation profiles in hemodialysis patients who were vaccinated against severe acute respiratory syndrome coronavirus 2, infected with the virus, or both, and compare them with those of dialysis patients in a control group.

Methods: Plasma samples from 112 hemodialysis patients were assigned to four groups: control, infected, vaccinated, and post-vaccine-infected. Paired plasma samples from 47 people with vaccination (vaccinees) were analyzed before and after the booster dose. The same analytical approach was applied to the four groups for a cross-sectional comparison.

Results: Our study found that both vaccination and infection groups showed decreased fucosylation of IgG1, which is associated with a proinflammatory biosignature. However, vaccination also leads to increased galactosylation and bisection of IgG antibodies, which are associated with anti-inflammatory effects and the additional regulation of immune responses. In contrast, infection led to an additional decrease in the fucosylation of IgG2 and IgA, demonstrating a more intense proinflammatory biosignature than vaccination.

Conclusions: Our findings emphasize the proinflammatory biosignature of afucosylation in both vaccination and infection groups. Additionally, we uncovered further regulated profiles related to galactosylation in vaccinees. These findings suggest that antibody investigation for vaccination or infection should not solely focus on neutralization but should also consider effector function-related glycosylation profiling. This comprehensive information can be valuable for fine-tuning vaccine development in the future.