Asthma is a heterogeneous disease characterized by chronic airway inflammation. CD4(+) T-helper 9 (Th9) cells are closely linked to asthma, helping to regulate inflammation and immunity. Epidemiological studies showed that mycobacteria infections are negatively associated with asthma. Our previous research showed that inactivated Mycobacterium phlei nebulization alleviated the airway hyperresponsiveness and inflammation of asthma. However, the relationship between Th9 cells and mycobacteria remains unknown. Here, we evaluated the relationship between Mycobacterium vaccae nebulization and Th9 cells in asthmatic mice. Eighteen Balb/c mice were randomized into 3 groups of 6 mice each (normal control group, asthma control group, and nebulization asthma group [Neb. group]). The Neb. group was nebulized with M. vaccae one month before establishment of the asthmatic model with ovalbumin (OVA) sensitization, and the normal and asthma control groups were nebulized with phosphate-buffered saline. The hyperresponsiveness of the mouse airways was assessed using a non-invasive lung function machine. Lung airway inflammation was evaluated by hematoxylin and eosin and periodic acid-Schiff staining. Cytokine interlukin-9 (IL-9) concentration and OVA-specific IgE in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assays. The percentages of γδTCR+ CD3+, IL-9+CD3+, IL-10+CD3+ lymphocytes, and IL9+γδT and IL-10+γδT cells were detected by flow cytometry. The airway inflammation and concentration of IL-9 and OVA-specific IgE were significantly reduced in the Neb. group compared to the asthma control group. The Neb. group had lower airway hyperresponsiveness, percentages of γδTCR+CD3+ and IL-9+CD3+ lymphocytes, and IL9+γδT cells, and higher percentages of IL-10+CD3+ lymphocytes and IL-10+γδT cells compared to the asthma control group. Thus, mouse bronchial asthma could be prevented by M. vaccae nebulization. The mechanism could involve M. vaccae-mediated effects on induction of IL-9 secretion and suppression of IL-10 secretion from γδT cells. γδT cells showed prominent IL-10 expression, indicating that they possibly belong to the Th9 family.

Allergic asthma is a chronic airway disorder characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). A murine model of asthma was used to examine the antiasthmatic effect of inhaled inactived Mycobacterium phlei (M. phlei). AHR, neutrophil levels, eosinophil levels and levels of interleukin (IL)-17 and IL-23 receptor (IL-23R) were monitored. The results demonstrated that inactivated M. phlei alleviates the IL-17+γδT cell-mediated immune response and attenuates airway inflammation and airway hyperresponsiveness in the asthmatic murine lung, partially through inhibiting the expression of IL-23R. In conclusion, inactivated M. phlei may be an effective antiasthmatic treatment, regulating IL-17-producing γδT (IL-17+γδT) cell-mediated airway inflammation and airway hyperresponsiveness to relieve the symptoms of mice with asthma.

Purpose The Hippo signaling pathway participates in the restriction of cell proliferation and organ growth. Activated macrophages have been implicated in the pathogenesis of allergic asthma. Recent studies have shown that Hippo signaling pathway may also be involved in the regulation of asthma. However, the link between Hippo signaling pathway and macrophages in the context of allergic asthma has not been investigated. The purpose of this study was to explore the link between Hippo signaling pathway and macrophages using a mice model of OVA-induced allergic asthma. Methods Mice models of asthma were established. Lung tissues were collected from mice and pooled for mRNA sequencing and bioinformatics analysis. The relative mRNA expression of Hippo signalling pathway-related proteins Yap1, Lef1 and Ctgf was also measured. Double immunofluorescence staining was performed on lung tissues to evaluate macrophage marker F4/80 expression and Yap1/Lef1/Ctgf expression. Results Results of the RNA-Seq of lung tissues demonstrated that the Hippo signaling pathway was down-regulated in OVA-induced allergic asthma. Using the cytoHubba tool kits in Cytoscape, the following top 10 hub genes of Hippo signalling pathway were identified: Yap1, Lef1, Ctgf, Ccnd1, Axin2, Smad7, Wnt4, Wnt3a, Pard6b, and Wwc1 . Using the seq-ImmuCC ( http://218.4.234.74:3200/immune/ ), a negative correlation was found between macrophages and Hippo signaling pathway activity (R 2 = 0.93). The mRNA expression levels of pulmonary Yap1, Lef1, and Ctgf were down-regulated in the mice model of OVA-induced allergic asthma. Moreover, double-stained immunofluorescence for F4/80 and Yap1, Lef1, Ctgf in mouse lung sections respectively revealed that macrophage proliferation was correlated with downregulation of the Hippo signaling pathway in the mice model of OVA-induced allergic asthma. Conclusion These results demonstrated that the Hippo signaling pathway was down-regulated in asthma mice, and the proliferation of macrophages was associated with downregulation of the Hippo signaling pathway. These findings reveal novel insights into the pathogenesis and treatment of asthma.

Background: Mycobacterium vaccae nebulization imparted protective effect against allergic asthma in a mouse model. The TGF-β/Smad signal transduction pathway plays an important role in allergic bronchial asthma. However, the effect of M. vaccae nebulization on the TGF-β/Smad signal transduction pathway in mouse models of allergic asthma remains unclear. This study investigated the preventive effect of M. vaccae nebulization during bronchial asthma in a mouse model and elucidate the implication of TGF-β/Smad signal transduction pathway in the process. Methods: In total, 24 female Balb/c mice were randomized to normal control (group A), asthma control (group B), and M. vaccae nebulization (group C) groups. Both groups B and C were sensitized using ovalbumin for establishment of the asthmatic model; group A received phosphate-buffered solution. Prior to the establishment of asthma, Group C was nebulized with M. vaccae. Airway responsiveness was measured in all the groups, using a noninvasive lung function machine before and 24 h after establishment of the asthmatic model. The animals were then harvested, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The total cell counts in BALF was estimated. Protein expression of TGF-β1, TβR1, Smad1, and Smad7 was detected by immunohistochemistry. The population of CD3 + γδT, IL-13 + CD3 + T, TGF-β + CD3 + T, IL-13 + CD3 + γδT, and TGF-β + CD3 + γδT cells were detected by flow cytometry. One-way analysis of variance for within-group comparisons, the least significant difference t-test or Student-Newman-Keuls test for intergroup comparisons, and the nonparametric rank sum test for analysis of airway inflammation scores were used in the study. Results: The eosinophil count; protein expression of TGF-β1, TβR1, and Smad1; and percentages of CD3 + γδT and IL-13 + CD3 + T cells were significantly lower in the M. vaccae nebulization group than in the asthma control group (P < 0.01). There were significant intergroup differences in the percentages of TGF-β + CD3 + T and IL-13 + CD3 + γδT cells (P < 0.05). Conclusions: Mycobacterium vaccae nebulization could confer protection against allergic bronchial asthma by reducing airway responsiveness and alleviating airway inflammation in mice. The underlying mechanism might be attributed its effect on the deregulated expression of TGF-β1, TβR1, Smad1, and Smad7 of the TGF-β/Smad signal transduction pathway.

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Background. Upper respiratory tract infections (URTIs) are common and burdensome infectious illness. Several trials have reported that probiotics can prevent URTIs in adults. Objectives. To evaluate the efficacy and safety of probiotics in the prevention of URTIs in adults. Methods. PubMed, Web of Science, Embase, and Cochrane Library were searched for reports published from database inception to May 14, 2020. Randomized controlled trials (RCTs) comparing probiotics with placebo for the prevention of URTIs in adults were included. Results. Six RCTs with 1551 participants were included. Compared with the placebo group, the probiotics intervention group significantly reduced the incidence of URTI episodes (RR: 0.77; 95% CI: 0.68 to 0.87; P < 0.0001 ; I2 = 26%), the episode rate of URTIs (rate ratio: 0.72; 95% CI: 0.60 to 0.86; P = 0.0002 ; I2 = 99%), and the mean duration of one episode of URTI (MD: −2.66; 95% CI: −4.79 to −0.54; P = 0.01 ; I2 = 80%). The adverse events of probiotics were mainly mild gastrointestinal symptoms. There were no significant differences in occurrence rate of adverse effects between probiotics intervention and placebo group (rate ratio: 1.01; 95% CI: 0.80 to 1.26; P = 0.96 ; I2 = 99%). Conclusion. Low-quality evidence provides support that probiotics have potential efficacy for preventing URTI episodes in adults. More trials are required to confirm this conclusion.

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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 antiinflammatory treatment of smoking-related COPD/emphysema.