Critical Reviews in Immunology最新文献

Neonatal candidiasis poses significant clinical challenges due to its potential for severe morbidity and mortality in vulnerable infants. Due to their underdeveloped immune system, neonates are at a higher risk for infections caused by Candida species. They can vary from mild to severe, including penetrating deep tissues, bloodstream spread, and dissemination to organs. The immune system of newborns is marked by a limited innate immune response, with lower levels of pro-inflammatory cytokines. Adaptive immunity, important for lasting protection, also experiences delayed maturation with weakened Th1 and Th17 responses. These shortcomings result in a higher vulnerability to Candida infections during infancy. Murine models have been crucial in understanding the reasons behind this susceptibility. These models assist in examining how different immune elements, like neutrophils, macrophages, and T cells, and their interactions are involved in Candida infections. Moreover, they offer an understanding of how early-life exposure to Candida affects immune responses and may aid in developing possible therapeutic plans. In this article we review current results from research to provide a thorough summary and critical insights into neonatal immune response to Candida, highlighting the importance of using murine models in this field of study. Understanding these immune dynamics is essential for creating specific treatments and preventive strategies to prevent newborns from Candida infections, ultimately improving neonatal health outcomes.

Genetic polymorphisms in genes that enable the production of an effective host immune response, such as single nucleotide polymorphisms (SNPS) in the IL-6, INF-alpha, IFN-gamma, IL-10, TGF-beta genes can cause unfavorable clinical conditions or susceptibility to pathologies. The objective of this work is to evaluate the epidemiological and genetic profile of professionals from health institutions during the first pandemic wave. A case-control study was performed with convenience sampling from health institutions (HI) workers from Belém-PA, Northern Brazil (N = 213), divided into symptomatology groups (Asymptomatic-AS, n = 91; and Symptomatic-SI, n = 122); and severity groups classified by chest computerized tomography-CCT data (symptomatic with pulmonary involvement-SCP, n = 37; symptomatic without pulmonary involvement-SSP, n = 8). Genotyping was performed by sanger sequencing for SNP TNF-α -308 G/A (rs1800629), IFN-γ +874 T/A (rs2430561), TGF-β codon 10 (rs1982073), codon 25 (rs1800471), IL-6 - 174 G/C (rs180079), IL-10 - 1082 A/T (rs1800896), -819 C/T (rs1800871), and -592 A/C (rs1800872), and statistical analysis through the Epilfo program. Significant association was observed between the presence of comorbidities and poor prognosis of COVID-19 (especially between COVID-19 and overweight and obesity). Only the TNF-α 308 G/A snp was significantly associated with the symptoms and severity of COVID-19. These findings about this TNF-α SNP passed in the multiple testing correction at a false discovery rate (FDR)< 0.05. These data can help medicine and the scientific community understand the influence of genetics and epidemiological parameters in combating COVID-19.

Nasopharyngeal carcinoma (NPC), a malignant tumor originating from the epithelium and glands. MicroRNAs (miRNAs) play an essential role in the tumorigenesis and metastasis of NPC. They are effective biomarkers in the detection of malignant progression of NPC. In this study, we analyzed the expression profiles of miRNAs in NPC patients with Gene Expression Omnibus (GEO) database. ceRNA networks of NPC were constructed and target miRNAs were screened. MTT, colony formation and Transwell experiments were used to explore the effects of miR-205-5p on the proliferation, migration and invasion ability of NPC cells. Bioinformatics analysis combined with Double luciferase experiment verified the binding relationship between miR-205-5p and CALM1. We identified 34 long non-coding RNAs (lncRNAs), 22 miRNAs, and 145 messenger RNAs (mRNAs) and constructed a competing endogenous RNAs (ceRNA) network to explain the relationship between RNA expression profiles and NPC progression. Of which, we found that 5 miRNAs (hsa-let-7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-143-3p and hsa-miR-205-5p) are related to clinical features. We further found that miR-205-5p was highly expressed in NPC cell lines. In addition, MTT, colony formation and Transwell assays showed that miR-205-5p promoted the proliferation, migration and invasion of NPC cells. Double luciferase detection showed that miR-205-5p could target combined with CALM1. In addition, we found that miR-205-5p could promote the proliferation, migration and invasion of NPC cells by inhibited the expression of CALM1. Overall, the present study demonstrated that as a carcinogenic factor, miR-205-5p can affect the malignant progression of NPC by mediating CALM1.

Immunotherapy has shown significant promise in the clinical management of prostate cancer (PCa), and prostaglandin E receptor 4 (EP4) is a key governing factor in PCa progression. However, the molecular mechanisms by which EP4 influences immunotherapy in PCa have yet to be elucidated. This investigation was designed to unravel the specific mechanisms through which EP4 affects the killing ability of CD8+ T cells against PCa cells. Immunohistochemistry was utilized to assay the expression of EP4, programmed death ligand 1 (PD-L1), and CD8+ T cell infiltration in tissue samples, and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to evaluate EP4 expression in cells. PCa cell lines with either EP4 knockdown or overexpression were co-cultured with CD8+ T cells. Lactase dehydrogenase toxicity assays were employed to measure CD8+T cell killing ability, and ELISA was employed to measure interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) levels. Expression of T cell exhaustion markers was detected by flow cytometry. Rescue experiments were conducted utilizing 3-methyladenine [a phosphoinositide 3-kinase (PI3K) inhibitor] and PD-L1 knockdown. The impact of EP4 overexpression on the PI3K/AKT signaling pathway-mediated PD-L1 expression and its subsequent modulation of CD8+ T cell killing ability against PCa cells was assessed through qRT-PCR, WB, flow cytometry, and immunofluorescence. EP4 exhibited a substantial upregulation in both PCa tissues and cells, displaying a positive correlation with PD-L1 expression and a converse negative correlation with the infiltration of CD8+ T cells. Knockdown of EP4 expression inhibited CD8+ T cell exhaustion, enhanced CD8+ T cell killing ability against PCa cells, increased the levels of IFN-γ, IL-2, and TNF-α, and decreased PD-L1 expression. Conversely, EP4 overexpression resulted in opposite effects, but treatment with 3-methyladenine mitigated EP4-induced promotion of PD-L1, p-AKT, and t-AKT expression. Furthermore, the knockdown of PD-L1 mitigated the inhibitory impact of EP4 overexpression on the killing ability of CD8+ T cell and the levels of IFN-γ, IL-2, and TNF-α, all while leaving the expression of p-AKT and t-AKT unaffected. EP4 was significantly overexpressed in PCa and activated PD-L1 expression via the PI3K/AKT signaling pathway, thereby suppressing the activity of CD8+ T cells.

Background: Sarcoidosis is a complex inflammatory disease of unknown etiology affecting mostly the lungs and poses a significant diagnostic challenge, particularly in regions where tuberculosis (TB) is endemic. The diagnostic complexity intensifies due to shared clinical and radiological features between sarcoidosis and TB, as well as similarities with idiopathic pulmonary fibrosis (IPF) in cases that progress to pulmonary fibrosis. Accurately distinguishing between these diseases is critical for timely and effective patient management.

Objective: This study breaks new ground by evaluating the diagnostic power of the bronchoalveolar lavage (BAL) CD4/ CD8 ratio, along with key activation and memory markers to differentiate sarcoidosis from TB, IPF, and other-interstitial lung diseases (ILDs).

Methods: A cohort of 68 patients with ILDs, including sarcoidosis (n = 37), TB (n = 19), IPF (n = 6), and Other-ILDs (n = 6) were assessed. The CD4/CD8 ratio and a panel of activation and memory markers were analyzed through flow cytometry.

Results: Sarcoidosis exhibited a significantly higher CD4/CD8 ratio compared to those with TB, IPF, and Other-ILDs. An optimal cutoff value of 3.7 for the CD4/CD8 ratio in sarcoidosis with an area under the ROC curve (AUC) of 0.7%, had a specificity of 96.8%, and a sensitivity of 43.2%. In addition, a significant difference was detected in CD38, CD45RA, CD45RO, and CD62L expression.

Conclusion: Combining the CD4/CD8 ratio (> 3.7) with the expression of CD38, CD62L, and memory markers is a promising new tool for the differential diagnosis of sarcoidosis.