Yi-Qun Kuang

Mucosal‐associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate‐like T lymphocytes that are restricted by major histocompatibility complex Class I‐related (MR1) molecules. They can be activated either in a T‐cell receptor–MR1‐ or cytokine‐dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individuals, MAIT cells maintain mucosal barrier integrity, participate in tissue repair after injury, and prevent excessive inflammation. In microbial infections, MAIT cells eliminate infected cells and modulate immune responses or become pathogenic when overactivated by superantigens. In the context of immune‐related diseases, MAIT cells migrate to inflamed tissues and become pathogenic by secreting tissue‐damaging cytokines or protective by modulating immune responses. Moreover, MAIT cells have been demonstrated to have therapeutic applications in controlling diseases through their use as cellular adjuvants, their increased activation by engineered bacteria, and their modification with chimeric antigen receptors. This review synthesizes the functional plasticity of MAIT cells in health and disease, highlighting the therapeutic efficacy and limitations of engineered MAIT cells for precise intervention.

Chlamydia trachomatis ( C. trachomatis ) and Neisseria gonorrhoeae ( N. gonorrhoeae ) are common sexually transmitted pathogens. Although frequently asymptomatic, they can cause severe reproductive complications (e.g., epididymitis, salpingitis, pelvic inflammatory disease, and infertility) if untreated. We developed a duplex high-fidelity loop-mediated isothermal amplification (HiFi-LAMP) assay for simultaneous detection of C. trachomatis and N. gonorrhoeae . The assay demonstrated high sensitivity and specificity, with limits of detection (LODs) of 358 and 30 copies per 25 μL reaction for C. trachomatis and N. gonorrhoeae , respectively. The performance of the assays was evaluated by comparing with the commercial singleplex qPCR assays using 156 paired urine and genital secretion samples. The assays have 100% specificity across all samples and achieved 100% sensitivity for the detection of N. gonorrhoeae in urine and C. trachomatis in genital secretion samples and 98.7% and 88.5% sensitivity for N. gonorrhoeae in genital secretions and C. trachomatis in urines, respectively. Extraction-free HiFi-LAMP assays directly using a small amount of simply treated urine were established and showed 87.9% sensitivity and 100% specificity for the detection of N. gonorrhoeae in 70 urine samples. The new HiFi-LAMP assays can detect all C. trachomatis - and/or N. gonorrhoeae -positive samples within 30 min, implying that the entire HiFi-LAMP assay (including sample process) can be completed within 40 min, significantly shorter than about 90 min by the qPCR assays. The new HiFi-LAMP assays provide a rapid, simple, and cost-effective point-of-care testing (POCT) tool for clinical detection and/or surveillance of C. trachomatis and N. gonorrhoeae in resource-limited settings. IMPORTANCE: Asymptomatic C. trachomatis and N. gonorrhoeae infections significantly increase the risk of silent transmission. C. trachomatis and N. gonorrhoeae were cocirculating in sexually active individuals. Of 156 individuals, we detected 7 (4.5%) individuals positive for both C. trachomatis and N. gonorrhoeae , implying an urgent need for rapid accurate and duplex POCT assay for timely detection of C. trachomatis and N. gonorrhoeae . The development of a duplex HiFi-LAMP assay enables the simultaneous detection of C. trachomatis and N. gonorrhoeae with high sensitivity and specificity. The assay offers high diagnostic concordance with commercial qPCR assays and has lower cost and shorter reaction time. Given the availability of various portable fluorescent thermal cyclers and/or isothermal fluorimeters, the development of extraction-free HiFi-LAMP assay directly using simply treated urine will lower the barriers of sexually active individuals to routine screening and facilitate clinical detection and surveillance of C. trachomatis and N. gonorrhoeae in resource-limited settings.

Scabetic nodules are a cutaneous hypersensitivity reaction to scabies mites and their byproducts, often accompanied by persistent pruritus. These nodules remain a therapeutic challenge due to the lack of effective treatments. We sought to assess the effectiveness and tolerance of thalidomide for genital scabetic nodules. We performed a retrospective evaluation of thalidomide treatment (50-200 mg/day for 2-3 consecutive weeks) in 38 male patients with genital nodular scabies who had previously been infested with scabies mites and were left with persistent pruritic nodules on the genitals. A total of 38 male patients (age range: 18-40 years; mean age: 28.2 ± 5.79 years) with post scabetic nodules were included. Some of them had been refractory to other forms of therapy. Of the 38 patients, 28 patients (73.7%) showed nodule resolution after 2 weeks of treatment. A significant reduction in the number of nodules was observed at the end of the three-week treatment period (P < 0.05), and there was no sign of relapsing. Meanwhile, after two weeks of thalidomide treatment, the patient's pruritus symptoms significantly improved, manifested as a significant decrease in VAS (P < 0.05), and after three weeks of treatment, VAS further significantly decreased (P < 0.05). Infrequent adverse events, including rash, mild dizziness, and/or drowsiness, occurred in nine patients and resolved after drug withdrawal. Thalidomide may be a promising option for treating refractory scabies nodules. Not applicable.

Background: Deep fungal infections (DFIs) represent a significant and growing threat to hospitalized patients, contributing to substantial morbidity and mortality worldwide. The healthcare landscape has undergone notable changes in recent years, particularly with the impact of the COVID-19 pandemic, which has altered host immunity and care pathways, potentially influencing the epidemiology of DFIs. Objective: This study aimed to delineate the clinical characteristics, mycological profiles, risk factors of deep fungal infections, and to evaluate factors associated with mortality among inpatients in a general hospital in southwestern China from 2020 to 2024. Methods: This was a retrospective analysis of 886,056 patients in the hospital from 2020 to 2024, including the epidemiological characteristics, treatment, and prognosis of deep fungal infections. Results: A total of 462 cases (0.052%) with deep fungal infections were identified, accounting for 0.052% of the total number of hospitalizations. The incidence of deep fungal infections in the hospital showed an increasing trend from 2020 to 2024. Compared with previous studies, Candida remained the predominant pathogen (84.20%), with increased proportions of Aspergillus (13.90%) and Cryptococcus (6.71%). A new case of Mucor infection (0.22%) was reported. The respiratory tract remains the most common site of infection (88.60%). In terms of treatment, most patients received azole therapy (88.30%), with those treated with echinocandins showing significantly higher survival rates ( P = 0.033). Multiple logistic regression analyses revealed that mixed infections, hematologic diseases, and biological agents were significant risk factors for poor prognosis (all P < 0.05). Conclusions: Compared with earlier research (2015–2019), the number of deep fungal infection cases from 2020 to 2024 has shown a significant and sustained increase. Moreover, the threat posed by Aspergillus and Cryptococcus has increased. Although clinical data remain limited, these findings provide valuable insights for the prevention, diagnosis, and treatment of deep fungal infections. Compared with earlier research (2015–2019), the number of deep fungal infection cases from 2020 to 2024 has shown a significant and sustained increase. Moreover, the threat posed by Aspergillus and Cryptococcus has increased. Although clinical data remain limited, these findings provide valuable insights for the prevention, diagnosis, and treatment of deep fungal infections.

Candida glabrata often resides within macrophages, creating challenges for antifungal treatment. This study investigates the impact of antifungal agents on the immune response of C. glabrata within macrophages to understand its immune evasion mechanisms. Standard C. glabrata strains ATCC2001 and a clinical strain (17K1152) were pretreated with micafungin (MCF), itraconazole (ICZ), and amphotericin B (AmB) for 24 hours and then co-cultured with macrophages for 6, 12, 24, and 48 hours. Transmission electron microscopy (TEM) analysis was performed, and cytokine levels (interleukin [IL]-6, granulocyte-macrophage colony-stimulating factor [GM-CSF]) were measured using enzyme-linked immunosorbent assay kits. C. glabrata showed the greatest susceptibility to MCF, followed by AmB, with ICZ having the least effect. TEM analysis revealed MCF-induced damage to both the cell wall and membrane, whereas AmB disrupted only the membrane. ICZ showed less noticeable damage. MCF-pretreated yeast cells were more readily damaged in macrophages than those pretreated with AmB or ICZ. IL-6 secretion patterns were similar in untreated and ICZ-treated groups, while AmB initially decreased IL-6 secretion before recovery, and MCF consistently increased IL-6 levels. GM-CSF secretion showed comparable trends for untreated and ICZ groups, with MCF and AmB exhibiting fluctuations. Echinocandins enhanced macrophage immune activity by modifying C. glabrata ’s cell wall and increasing pro-inflammatory cytokine secretion, impairing its survival within host cells. Azole pretreatment had minimal impact on yeast replication and survival, reflecting resistance. Polyenes-treated yeast evade innate immunity by reducing pro-inflammatory cytokine secretion and modulating macrophage recruitment. IMPORTANCE: Candida glabrata is a major cause of bloodstream infections and is often resistant to antifungal treatment. Understanding how different antifungal drugs affect its survival within macrophages is critical for improving therapy. This study demonstrates that echinocandins enhance macrophage-mediated killing by damaging the fungal cell wall and increasing pro-inflammatory cytokine secretion, whereas azoles have minimal effect, and polyenes may aid immune evasion. These findings provide mechanistic insights into antifungal resistance and host-pathogen interactions, informing strategies for more effective treatment of C. glabrata infections.

Incomplete immune reconstitution occurs in 10%-40% of antiretroviral therapy (ART)-treated human immunodeficiency virus 1 (HIV-1) patients. This subset of immunological non-responders (INRs) has yet to undergo a comprehensive analysis of immunological profiles, and no definitive cytological diagnosis has been established. In this study, we comparatively analyzed the immunological profiles of INRs, immunological responders (IRs), and healthy control individuals (HCs) via single-cell RNA sequencing (scRNA-seq) and single-cell T-cell receptor (TCR) repertoire sequencing of peripheral blood mononuclear cells (PBMCs), and identified a relatively small population of mucosal-associated invariant T (MAIT) cells in INRs. This finding was recapitulated in rhesus macaques infected with simian immunodeficiency virus (SIV). Specifically, the population of the naïve MAIT cell subtype was significantly lower in INRs than in IRs, and the majority of MAIT cells were CD8⁺ cell subsets. Further characteristic analysis of MAIT cells via the transcriptome revealed decreased expression of cytotoxicity-related genes in INRs, while displaying increased expression of genes involved in TGF-β receptor signaling. In summary, by conducting a comparative analysis, this study revealed a correlation between the decreased proportion of naïve MAIT cells and impaired immune reconstitution in INRs. This finding highlights a particular cell subset that may play a pivotal role in the incomplete immune reconstitution, and suggests a plausible cellular target for the modulation of INRs.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (Mlep), and is classified as a tropical disease by the WHO. While prior research has documented the various phenotypes and functions of T cells and B cells in Mlep infection, the specific clonotypes of T cells and B cells that are essential for understanding the progression of multibacillary leprosy have not been reported. Here, we established a single-cell V(D)J sequencing dataset including 5 multibacillary leprosy patients (MBs) and 5 healthy individuals (HCs), aiming to generate comprehensive profiles of T-cell receptors and B-cell receptors present in the peripheral blood. This study suggested that Mlep infection has distinct selective effects on peripheral immune repertoires and that these biased immune repertoires observed in MBs have potential as biomarkers. This dataset provides very comprehensive and valuable data on the peripheral blood immune repertoire of multibacillary leprosy patients. It holds considerable importance in the clinical monitoring and management of Mlep infections, ultimately contributing to the WHO goal “Towards Zero Leprosy” by 2030.

Asthma is a chronic respiratory disease characterized by airway inflammation and immune cell imbalance. The transcription factor E26 transformation-specific-1 regulates immune cell functions, but its role in asthma remains unclear. Here, we generated Ets1 heterozygous (Ets1+/−) mice by constitutively knocking out exons 7 and 8 of Ets1, confirmed significantly reduced Ets1 expression via western blot. Asthma models were then established in both wild-type and Ets1+/− mice, revealing more severe pulmonary inflammation in Ets1+/− mice. Then, we systematically explored the regulatory effects of Ets1 on immune cells function and inflammatory responses in asthma. Further analyses showed enhanced CD4+ helper T (Th) 2/Th17 cell responses and elevated interleukin-4 and interleukin-17A secretion in the asthma Ets1+/− mice. By combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we identified 17 transcription factors regulated by Ets1 and linked to the function of mitotic processes in asthma. These findings suggest that Ets1 mitigates asthma by modulating CD4+ Th2/Th17 immune responses and regulating transcription factors associated with cell cycle processes.

Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate.