Mycobacteriosis, mostly resulting from
(MTb), nontuberculous mycobacteria (NTM), and
(
), 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.
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.
This is annular erythema on the face of a man in his 50s (fig 1). He presented with a six year history of an asymptomatic, well defined 12 cm diameter lesion that had been unresponsive to topical ...terbinafine. The patient had some loss of fine touch sensation and nociception, but peripheral nerves were not palpable or tender on examination. Histological examination revealed epithelioid granulomas without necrosis. Acid fast bacilli in skin smears and results from nested polymerase chain reaction and DNA sequencing confirmed Mycobacterium leprae. Borderline tuberculoid leprosy was diagnosed on the basis of clinical and laboratory findings.
The CC chemokine ligand 18 (CCL18) has a higher expression in some tumors, while the CCL18 level can be a marker of tumor progression and prognosis. We previously reported that the expression of ...CCL18 gene was dramatically up-regulated in cutaneous malignant melanoma (CMM) and its expression levels were correlated with tumor thickness.
To investigate miRNAs which could target the CCL18 gene so as to mediate CMM development and improvement.
The expression of miR-128 and CCL18 in CMM were measured by qRT-PCR. The interaction of miR-128 with CCL18 3′UTR was verified by Luciferase reporter gene assay. The changes in expression of CCL18 after miR-128 mimic transfection of A375 melanoma cells were determined by both qRT-PCR and Western-bloting. Cell viability was accessed by CCK8-assay. Flow cytometry was employed to detect the incidence of apoptosis. Clonogenic assay was used to detect the ability of colony formation. Cell migration was evaluated by Transwell migration study. The protein levels of epithelial-mesenchymal transition (EMT), such as E-cadherin, N-cadherin and β-catenin were analyzed by Western-bloting.
The expression of miR-128 had negative relevance with CCL18 in CMM. miR-128 could interact with CCL18 3′UTR. Transfected miR-128 mimic significantly reduced CCL18 expression and this impairment of CCL18 gene promoted apoptosis, inhibited migration and colony formation of A375 melanoma cells. Furthermore, the relative expression of N-cadherin was decreased.
CCL18 is a target gene of miR-128. Overexpression of miR-128 inhibits the oncogenic effect of CCL18.
To the Editor:
Wang et al. (May 18 issue)
1
report results of a 4-year trial that showed that the incidence of leprosy among household contacts was lower with single-dose rifapentine than with no ...intervention. Although the methods appear sound, several potential biases and concerns warrant attention. First, the short follow-up period challenges the plausibility of the findings, considering the estimated incubation period of leprosy of 5 to 20 years — which can even exceed 50 years, especially in areas with low endemic levels of the disease.
2
Second, single-dose rifapentine in combination with minocycline and moxifloxacin has been shown to delay . . .
•Local subsets and recirculation subsets of T cells in TB patients were firstly separately studied and compared.•The extent of lymphocyte diversity in peripheral blood impacted the immune outcomes of ...tuberculosis.•Combination of scTCR-seq and GLIPH2 algorithm helped vaccine development and novel antigen discovery.•Functions and specificity of local T cell subsets remained to be discovered.
T cell induced cellular immunity is considered to be extremely important for the control of tuberculosis (TB). T cell receptor (TCR), the key component responsible for the specificity and clustering of T cells, holds the potential to advance our understanding of T cell immunity against TB infection. This review systematically expounded the study progressions made in the field of TB-relevant TCRs based on single cell sequencing together with GLIPH2 technology and initiated a comparison of the T cell distribution between peripheral blood and infected organs. We divided clonal expanded T cell clones into recirculation subsets and local subsets to summarize their distinctions in clonal abundance, TCR sequences and antigenic specificity. Notably, local expansion appears to drive the primary variances in T cell subsets between these two contexts, indicating the necessity for further exploration into the functions and specificity of local subsets.
Background
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive malignancy which is diagnostically challenging.
Objectives
To characterize clinical, histopathological and ...immunophenotypic features of BPDCN with cutaneous involvement.
Materials & Methods
Cases of BPDCN with skin lesions diagnosed between 2010 and 2020 were retrospectively studied.
Results
The age at diagnosis presented a bimodal pattern. The morphological features of skin lesions of BPDCN were heterogeneous, manifesting as disseminated, sporadic or solitary plaques, nodules or tumours. Histopathologically, tumour cells in 67.9% of lesions infiltrated in a diffuse and nodular pattern. Interstitial, lichenoid and perivascular patterns were observed in 14.3%, 7.1% and 10.7% lesions, respectively. Angioinvasion and necrosis were absent. All tumour cells were lymphoblastic-like with polymorphic and irregular nuclei except for one lesion revealing monomorphous immunoblastic-like cells. Immunohistochemically, CD4, CD56, CD123 and TCL-1 were positive in 82.1%, 92.9%, 96.0% and 100% cases of BPDCN, respectively. Simultaneous expression of the four markers were observed in 65.0% of stained lesions. Notably, E2-2 was positively expressed in the nuclei of tumour cells in all BPDCN lesions, but was negative in all myeloid sarcoma lesions. Moreover, peripheral blood flow cytometry of six BPDCN cases revealed varying degrees of tumour cells with heterogeneous expression of CD56.
Conclusion
The morphological and phenotypic features of cutaneous BPDCN are heterogeneous. E2-2 may serve as a useful marker to definitively diagnose BPDCN
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