Granulysin-mediated reduction of PDZRN3 induces Cx43 gap junctions activity exacerbating skin damage in trichloroethylene hypersensitivity syndrome.

Trichloroethylene (TCE)-induced hypersensitivity syndrome (THS) has been a concern for many researchers in the field of environmental and occupational health. Currently, there is no specific treatment for THS, leaving patients to contend with severe infections arising from extensive skin lesions, consequently leading to serious adverse effects. However, the pathogenesis of severe skin damage in THS remains unclear. This study aims to investigate the specific danger signals and mechanisms underlying skin damage in THS through in vivo and in vitro experiments. We identified that cell supernatant containing 15 kDa granulysin (GNLY), released from activated CD3-CD56+NK cells or CD3+CD56+NKT cells in PBMC induced by TCE or its metabolite, promoted apoptosis in HaCaT cells. The apoptosis level decreased upon neutralization of GNLY in the supernatant by a GNLY-neutralizing antibody in HaCaT cells. Subcutaneous injection of recombinant 15 kDa GNLY exacerbated skin damage in the THS mouse model and better mimicked patients' disease states. Recombinant 15 kDa GNLY could directly induce cellular communication disorders, inflammation, and apoptosis in HaCaT cells. In addition to its cytotoxic effects, GNLY released from TCE-activated NK cells and NKT cells or synthesized GNLY alone could induce aberrant expression of the E3 ubiquitin ligase PDZRN3, causing dysregulation of the ubiquitination of the cell itself. Consequently, this resulted in the persistent opening of gap junctions composed of connexin43, thereby intensifying cellular inflammation and apoptosis through the "bystander effect". This study provides experimental evidence elucidating the mechanisms of THS skin damage and offers a novel theoretical foundation for the development of effective therapies targeting severe dermatitis induced by chemicals or drugs.

Unveiling the mechanisms of trichloroethylene hypersensitivity syndrome: Exploring the role of connexin 43 gap junctions in severe skin damage.

Trichloroethylene (TCE), extensively used as an organic solvent in various industrial applications, has been identified as a causative factor in inducing hypersensitivity syndrome (THS). Currently, there is no specific treatment for THS, and most patients experience serious adverse outcomes due to extensive skin damage leading to severe infection. However, the pathogenesis of THS-associated skin damage remains unclear. This study aims to elucidate the mechanism underlying skin damage from the perspective of intercellular communication and gap junctions in THS. Our results verified that hyperactivation of connexin43 gap junctions, caused by the aberrantly elevated expression of connexin43, triggers a bystander effect that promotes apoptosis and inflammation in THS via the TNF-TNFRSF1B and mitochondria-associated pathways. Additionally, we identified the gap junction inhibitor Carbenoxolone disodium (CBX) as a promising agent for the treatment of skin damage in THS. CBX protects against inflammatory cell infiltration in the skin and decreases immune cell imbalance in the peripheral blood of THS mice. Furthermore, CBX reduces connexin43 expression, apoptosis and inflammation in THS mice. The study reveals new insights into the mechanisms underlying TCE-induced skin damage, offering a potential treatment strategy for the development of effective therapies targeting severe dermatitis induced by chemical exposure.

Molecular epidemiological characteristics of Mycobacterium leprae in highly endemic areas of China during the COVID-19 epidemic.

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Spatiotemporal pattern of leprosy in southwest China from 2010 to 2020: an ecological study.

BACKGROUND: Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. METHODS: This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. RESULTS: A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: -14.0 to - 10.5; P < 0.001). Results of global spatial autocorrelation showed that leprosy cases presented clustering distribution in the study area. Most likely clusters were identified during the study period and were frequently located at Yunnan or the border areas between Yunnan and Guizhou Provinces. Secondary clusters were always located in the western counties, the border areas between Yunnan and Sichuan Provinces. CONCLUSIONS: Geographic regions characterized by clusters with high rates were considered as leprosy high-risk areas. The findings of this study could be used to design leprosy control measures and provide indications to strengthen the surveillance of high-risk areas. These areas should be prioritized in the allocation of resources.

Research on the descaling characteristics of a new electrochemical water treatment device.

In recent years, chemical water treatment equipment has gained significant attention due to its environmental-friendly features, multifunctionality, and broad applicability. Recognizing the limitations of existing chemical treatment equipment, such as challenges in scale removal and the high water content in scale deposits, we propose a novel drum design for both anode and cathode, enabling simultaneous scale suction and dehydration. We constructed a small experimental platform to validate the equipment's performance based on our model. Notably, under the optimal operating parameters, the hardness removal rate for circulating water falls within the range of 19.6-24.46%. Moreover, the scale accumulation rate per unit area and unit time reaches 13.7 g h-1 m-2. Additionally, the energy consumption per unit weight of the scale remains impressively low at 0.16 kWh g-1. Furthermore, the chemical oxygen demand (COD) concentration decreased from an initial 106.0 mg L-1 to a mere 18.8 mg L-1, resulting in a remarkable total removal rate of 82.26%. In conclusion, our innovative electrochemical water treatment equipment demonstrates exceptional performance in scale removal, organic matter degradation, and water resource conservation, offering valuable insights for future research and development in chemical treatment equipment and electrochemical theory.

Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

Genomic characteristics of Mycobacterium tuberculosis isolates of cutaneous tuberculosis.

Objectives: Cutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis. Methods: 58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection. Results: The M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites. Conclusions: The different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Comparative Evaluation of LAMP and Nested PCR for the Rapid Diagnosis of Mycobacterium marinum Infection.

Purpose: Culture of Mycobacterium marinum is very time-consuming, taking several weeks to produce positive results. Seeking rapid and sensitive diagnostic methods for diagnosis can greatly improve patient treatment. Our study aimed to compare the rapid diagnostic abilities of polymerase chain reaction (PCR), nested PCR and loop mediated isothermal amplification (LAMP) of detecting M. marinum in skin samples from patients with M. marinum infection. Methods: A total of 6 M. marinum strains and 6 skin samples with definite diagnosis of M. marinum infection were included in the study. We optimized LAMP performance for detection of M. marinum genomic DNA and confirmed the specificity of the primers. Then, the sensitivity of the LAMP and nested PCR assays were assessed by M. marinum strains and clinical samples. Results: Nested PCR was 10-fold more sensitive than the LAMP assay by serial dilution of M. marinum DNA. PCR positive samples were all positive by LAMP detection of 6 clinical M. marinum strains. Out of 6 clinical skin specimens confirmed as M. marinum infection, 0 (0%), 3 (50%), 3 (50%), and 4 (66.6%) were positive by PCR, nested PCR, LAMP and culture. The LAMP shared the same sensitivity than nested PCR in M. marinum strains and clinical samples, but it was easy to perform and faster than nested PCR assay. Conclusion: Compared with conventional PCR, LAMP and nested PCR are more sensitive and have a higher detection rate of M. marinum in clinical skin specimens. The LAMP assay proved to be more suitable for rapid diagnosis of M. marinum infection in a shorter time, especially in resource-limited settings.

Occupational health effect of TCE exposure: Experiment evidence of gene-environment interaction in hypersensitivity reaction.

BACKGROUND: Recently, Trichloroethylene (TCE) induced TCE hypersensitivity syndrome (THS) has attracted the attention of many researchers in the field of environmental and occupational health. Studies have revealed that Human leukocyte antigen (HLA) polymorphisms were the important genetic determinants of the diseases, but the potential molecular mechanism remains unclear. OBJECTIVE: This study aimed to investigate the association between THS and HLA at the molecular level. METHOD: We chose the human B-lymphoblastoid cell line Hmy2.C1R transfected with cDNA of HLA-B*13:01 and HLA-B*13:02 to analyze the characteristics of HLA-B-binding peptides and investigate the effect of TCE on the binding affinity of peptides to the HLA-B molecules. Further, the mathematical model was used to identify the possible interaction between TCE and HLA-B*13:01 or HLA-B*13:02 molecule. RESULTS: 54 HLA-B*13:01-binding peptides and 85 HLA-B*13:02-binding peptides were identified. Comparing the protein sequences of HLA-B*13:01 and HLA-B*13:02, amino acids were different at positions 94, 95 and 97. The results of the binding affinity of self-peptides to HLA molecules in the presence of TCE showed that TCE significantly decreased the binding affinity of peptides to HLA-B*13:01 only, but did not affect that of HLA-B*13:02. Molecular docking model showed that there was a unique high-affinity binding mode between TCE and HLA-B*13:01 (but not HLA-B*13:02), and the binding site located in the region of F pocket, suggesting that the unique structure of the F pocket of HLA-B*13:01 might provide the possibility of binding TCE. The pathogenesis of interaction between HLA-B*13:01 and TCE might belong to the model of the alteration of the HLA-presented self-peptide repertoire. DISCUSSION: This study explored the molecular mechanism of the association between THS and HLA-B*13:01, and had important implications for understanding the role of gene-environment interaction in the development of complex environment-related diseases.

Global prevalence of resistance to rifampicin in Mycobacterium leprae: A meta-analysis.

OBJECTIVES: As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions. METHODS: Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses. RESULTS: We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, -21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]). CONCLUSIONS: Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.

Functional and structural characteristics of HLA-B*13:01-mediated specific T cells reaction in dapsone-induced drug hypersensitivity.

BACKGROUND: Severe cutaneous adverse drug reactions (SCARs) are a group of serious clinical conditions caused by immune reaction to certain drugs. The allelic variance of human leukocyte antigens of HLA-B*13:01 has been strongly associated with hypersensitivities induced by dapsone (DDS). T-cell receptor mediated activation of cytotoxic T lymphocytes (CTLs) has also been suggested to play an essential role in pathogenesis of SCARs. However, HLA-B*13:01-DDS-TCR immune synapse that plays role in drug-induced hypersensitivity syndrome (DIHS) associated T cells activation remains uncharacterized. METHODS: To investigate the molecular mechanisms for HLA-B*13:01 in the pathogenesis of Dapsone-induced drug hypersensitivity (DDS-DIHS), we performed crystallization and expanded drug-specific CTLs to analyze the pathological role of DDS-DIHS. RESULTS: Results showed the crystal structure of HLA-B*13:01-beta-2-microglobulin (ß2M) complex at 1.5 Å resolution and performed mutation assays demonstrating that I118 or I119, and R121 of HLA-B*13:01 were the key residues that mediate the binding of DDS. Subsequent single-cell TCR and RNA sequencing indicated that TCRs composed of paired TRAV12-3/TRBV28 clonotype with shared CDR3 region specifically recognize HLA-B*13:01-DDS complex to trigger inflammatory cytokines associated with DDS-DIHS. CONCLUSION: Our study identified the novel p-i-HLA/TCR as the model of interaction between HLA-B*13:01, DDS and the clonotype-specific TCR in DDS-DIHS.

Facial Erythema Due to Lupus Vulgaris and Candida albicans Infections: A Case Report.

Co-infection of Mycobacterium tuberculosis (MTB) and Candida albicans with erythema on the face is rare. A familiar red spot on the face can easily lead to missed diagnosis and misdiagnosis. Untreated lupus vulgaris (LV) can form scar tissue. And the fungal infection that cannot be diagnosed and treated timely can also lead to failure of LV treatment, resulting in facial scarring, disfigurement, and psychological stress. In this study, we reported a case of a 58-year-old immunocompetent female co-infected with MTB and Candida albicans on her face. After anti-tuberculous and anti-fungal therapy, she recovered with no scar on her face.

Molecular Surveillance of Antimicrobial Resistance of Mycobacterium leprae from Leprosy Patients in Zhejiang Province, China.

Purpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province. Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy. Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases. Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.

Guanylate-Binding protein 2b regulates the AMPK/mTOR/ULK1 signalling pathway to induce autophagy during Mycobacterium bovis infection.

Autophagic isolation and degradation of intracellular pathogens are employed by host cells as primary innate immune defense mechanisms to control intercellular M. bovis infection. In this study, RNA-Seq technology was used to obtain the total mRNA from bone marrow-derived macrophages (BMDMs) infected with M. bovis at 6 and 24 h after infection. One of the differential genes, GBP2b, was also investigated. Analysis of the significant pathway involved in GBP2b-coexpressed mRNA demonstrated that GBP2b was associated with autophagy and autophagy-related mammalian target of rapamycin (mTOR) signaling and AMP-activated protein kinase (AMPK) signaling. The results of in vivo and in vitro experiments showed significant up-regulation of GBP2b during M. bovis infection. For in vitro validation, small interfering RNA-GBP2b plasmids were transfected into BMDMs and RAW264.7 cells lines to down-regulate the expression of GBP2b. The results showed that the down-regulation of GBP2b impaired autophagy via the AMPK/mTOR/ULK1 pathway, thereby promoting the intracellular survival of M. bovis. Further studies revealed that the activation of AMPK signaling was essential for the regulation of autophagy during M. bovis infection. These findings expand the understanding of how GBP2b regulates autophagy and suggest that GBP2b may be a potential target for the treatment of diseases caused by M. bovis.

Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis.

The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.

Insight into the Molecular Characteristics of Langhans Giant Cell by Combination of Laser Capture Microdissection and RNA Sequencing.

PURPOSE: The presence of Langhans giant cell (LGC) is a hallmark of mycobacterium-induced granuloma. The molecular characteristics and functions of LGC remain unclear to date. The study aimed to systematically characterize the molecular characteristics of LGC and reveal the potential functions. METHODS: Human LGCs were purified through laser capture microdissection (LCM) in vitro. RNA sequencing and in-depth transcriptome analysis were performed for purified LGCs and macrophages in the same system. Skin samples from mycobacterial infection patients were used to confirm some of the transcriptional expression. RESULTS: Human LGCs have different expression pattern from macrophages in the same in vitro system. A total of 967 differentially expressed genes were found. Bioinformatics analysis showed that LGCs are is characterized by active cell shape regulation, increased cytoskeletal components, weakened energy metabolism level, and reduced immune response. CCL7 may be a specific molecular for LGC to communicate with CCR1-expression cells in granuloma. CONCLUSION: LGCs have unique molecular characteristics different from that of macrophages. They may play a role in maintaining the hemostasis in granuloma.

Progress of the Art of Macrophage Polarization and Different Subtypes in Mycobacterial Infection.

Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

IFI44L as a Forward Regulator Enhancing Host Antituberculosis Responses.

Interferon-induced protein 44-like (IFI44L) gene is a type I interferon-stimulated gene (ISG) that plays a critical role in antiviral activity and constitutes a promising diagnostic marker. However, its precise role and function in tuberculosis have not been unveiled. This study showed that IFI44L acts as an antimicrobial target and positive modulator in human macrophages. Knockdown of IFI44L led to increased Mycobacterium tuberculosis intracellular survival. Moreover, IFI44L was significantly upregulated, and it restricted the intracellular survival of M. tuberculosis H37Rv strains at 72 h after rifampicin treatment. Individuals with cutaneous tuberculosis (CTB) were found to have significantly higher IFI44L expression after 6 months of rifampicin therapy than after only 1 month. These results demonstrated that IFI44L induced positive regulation and clearance of M. tuberculosis from human macrophages. This antimicrobial activity of IFI44L makes it a possible target for therapeutic applications against M. tuberculosis.