Co-Infection with Nocardia Terpene and Pneumocystis Jirovecii in a Patient with Anti-Synthetase Syndrome: A Case Report.

Background: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity. Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection. Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient's condition significantly improved. Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+ T cells in mice.

Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.

Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.

BACKGROUND: Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome-wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS-supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. METHODS: A case-control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). RESULTS: The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048-3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001-4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. CONCLUSION: rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

Association of IL1RL1 rs3771180 and TSLP rs1837253 variants with asthma in the Guangxi Zhuang population in China.

OBJECTIVE: IL-1 receptor-like 1 (IL1RL1) and thymic stromal lymphopoietin (TSLP) play important roles in asthma in various ways. IL1RL1 rs3771180 and TSLP rs1837253 single nucleotide polymorphisms (SNPs) are associated with asthma in some European nationals but not in Zhuang people. Accordingly, this study aimed to determine the associations of IL1RL1 rs3771180 and TSLP rs1837253 with asthma in Zhuang people. METHODS: We performed a case-control study to observe the association between the two polymorphisms and asthma in a Guangxi Zhuang cohort consisting of 123 asthmatic patients and 100 healthy controls. These individuals were recruited from the Department of Respiration of the First Affiliated Hospital of Guangxi Medical University. Multiplex PCR assay was used to identify the genotype of rs3771180 and rs1837253. Data were analyzed with SPSS 22.0 and SHEsis. RESULTS: rs1837253 showed significant differences between asthmatic and control groups in allele comparison (OR = 2.15; 95% CI = 1.27-3.63; P = 0.004), as well as in the homozygote (OR = 4.83; 95% CI = 1.47-16.47; P = 0.012), heterozygote (OR = 2.69; 95% CI = 1.20-6.00; P = 0.016), and dominant (OR = 3.01; 95% CI = 1.39-6.52; P = 0.005) genetic models. However, the genotype frequencies of rs3771180 did not obviously differ. CONCLUSION: rs1837253 is associated with asthma susceptibility and may increase the risk of asthma in Zhuang people in Guangxi.