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Background: Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. Materials and Methods: In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. Results: The mean age of patients was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients. [ABSTRACT FROM AUTHOR]

Background: Non−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients. Methods: Thirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)–restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry. Results: miR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=−0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype. Conclusions: The current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T), a rare inherited disorder, usually affects the nervous and immune systems, and occasionally other organs. A-T is associated mainly with mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a protein kinase that has a major role in the cellular response to DNA damage. We report here a novel ATM mutation (c.3244_3245insG; p.His1082fs) in an 11-year old female. This subject presented with typical features, with the addition of chest manifestations including mediastinal lymphadenopathy and diffuse bilateral micronodular infiltration of the lungs, along with a high EBV titer. The subject died as a result of rapid B-cell lymphoma progression before chemotherapy could be initiated. This case highlights the need for the rapid diagnosis of A-T mutations and the detection of associated life-threatening outcomes such as cancers. [ABSTRACT FROM AUTHOR]

The article discusses the diagnosis of sarcoidosis in patients with tuberculosis (TB). Topics include two TB-related conditions, body defenses against TB, and the risk of developing sarcoidosis by TB patients. Also provided is information regarding several diagnostic tests with combinations of mRNA, microRNA, and genetics profiles to improve phenotyping of sarcoid patients.

Extracellular ATP is a signaling molecule which plays an important role in alerting the immune system in case of any tissue damage. Recent studies show that binding of ATP to the ionotropic P2X7 receptor of inflammatory cells (macrophages and monocytes) will induce caspase 1 activation. Stimulation of caspase 1 activity results in maturation and release of IL-1β in the inflammasome in Chronic Obstructive Pulmonary Disease (COPD) patients. COPD is an inflammatory disease characterized by emphysema and/or chronic bronchitis and is mostly associated with cigarette smoking. It is one of the leading causes of death in humans and there is currently no medication to stop the progression of disease. A deeper understanding of the mechanism by which the P2X7 receptor triggers IL-1β maturation and release, may open new opportunities for the treatment of inflammatory diseases such as COPD. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular ATP is a signaling molecule that often serves as a danger signal to alert the immune system of tissue damage. This molecule activates P2 nucleotide receptors, that include the ionotropic P2X receptors and metabotropic P2Y receptors. Recently, it has been reported that ATP accumulates in the airways of both asthmatic patients and sensitized mice after allergen challenge. The role and function of ATP in the pathogenesis of chronic obstructive pulmonary diseases (COPD) are not well understood. In this study we investigated the effect of cigarette smoke on purinergic receptors and ATP release by neutrophils. Neutrophils and their mediators are key players in the pathogenesis of lung emphysema. Here we demonstrated that in an in vivo model of cigarette smoke-induced lung emphysema, the amount of ATP was increased in the bronchoalveolar lavage fluid. Moreover, activation of neutrophils with cigarette smoke extract induced ATP release. Treatment of neutrophils with apyrase (catalyses the hydrolysis of ATP to yield AMP) and suramin (P2-receptor antagonist) abrogated the release of CXCL8 and elastase induced by cigarette smoke extract and exogenous ATP. These observations indicate that activation of purinergic signaling by cigarette smoke may take part in the pathogenesis of lung emphysema. [Copyright &y& Elsevier]

Objective: Mast cells play pivotal roles in immediate-type and inflammatory allergic and nonallergic reactions. Cross-linking of the high-affinity receptor for IgE (FcεRI) on mast cells activates a signaling pathway leading to Ca2+ mobilization and is followed by degranulation and the release of histamine and other preformed mediators, as well as de novo synthesis of arachidonic acid metabolites. In a previous study, we have demonstrated that heat shock activates heat shock transcription factor-1 (HSF-1), induces heat shock protein 70 (HSP70), and suppresses cytokine production in bone marrow–derived mast cells (BMMC). In this study, we further investigated the effects of heat shock on the activation of mast cells and the release of mast cell mediators. Methods: In mouse mast cells, derived from a culture of bone marrow cells of male BALB/cBy and null HSF-1−/−mice, responsiveness to heat shock was monitored by measuring β-hexosaminidase and leukotriene C4 (LTC4) release. Results: Using BMMC, we found that heat shock inhibits degranulation of BMMC without affecting leukotriene production. To further elucidate the mechanism of suppression of degranulation, we studied the effects of heat shock on the regulation of signal transduction in more detail. We found that heat shock inhibits calcium mobilization and tyrosine phosphorylation of Syk and SHIP upon IgE receptor activation, but increases the phosphorylation of SHP-1 and -2. Moreover, our results revealed that suppression of tyrosine phosphorylation of Syk and SHIP coincided with an increased tyrosine phosphatase activity. Conclusion: The inhibitory action of heat shock toward mast cell degranulation is likely due to shifting the balance between kinase and phosphatase activity. [Copyright &y& Elsevier]

Background: Genetic mutations that reduce intracellular superoxide production by granulocytes causes chronic granulomatous disease (CGD). These patients suffer from frequent and severe bacterial and fungal infections throughout their early life. Diagnosis is usually made in the first 2 years of life but is sometimes only diagnosed when the patient is an adult although they may have suffered from symptoms since childhood.Case Presentation: A 26-year-old man was referred with weight loss, fever, hepatosplenomegaly and coughing. He had previously been diagnosed with lymphadenopathy in the neck at age 8 and prescribed anti-tuberculosis treatment. A chest radiograph revealed extensive right-sided consolidation along with smaller foci of consolidation in the left lung. On admission to hospital he had respiratory problems with fever. Laboratory investigations including dihydrorhodamine-123 (DHR) tests and mutational analysis indicated CGD. Stimulation of his isolated peripheral blood neutrophils (PMN) with phorbol 12-myristate 13-acetate (PMA) produced low, subnormal levels of reactive oxygen species (ROS). Aspergillus terreus was isolated from bronchoalveolar lavage (BAL) fluid and sequenced.Conclusions: We describe, for the first time, the presence of pulmonary A. terreus infection in an adult autosomal CGD patient on long-term corticosteroid treatment. The combination of the molecular characterization of the inherited CGD and the sequencing of fungal DNA has allowed the identification of the disease-causing agent and the optimal treatment to be given as a consequence. [ABSTRACT FROM AUTHOR]

Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species. Having recognized microbial antigens, TLRs conduct the immune response towards a pro- or anti-allergy response. As a double-edged sword, they could initiate either harmful or helpful responses by the immune system in case of allergic asthma. In the current review, we will describe the role of TLRs and their signaling pathways in allergic asthma. [ABSTRACT FROM AUTHOR]