A Moonlighting Protein Secreted by aNasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium.Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

The Potential Factors and the Outcomes of Hypotensive Patients after Emergent Endotracheal Intubation

PURPOSE: Hypotension after emergency endotracheal intubation (ETI) is one of the major complications from emergency airway management. The aim of this study was to determine the possible risk factors that may predict postintubation hypotension (PIH) and its impact on in-hospital mortality. METHODS: We conducted a retrospective, standardized chart review of consecutive emergency department patients that required intubation between January 2011 and December 2014. Patients were divided into 2 groups according to the presence or absence of PIH. PIH was defined as any recorded systolic blood pressure with less than 90 mmHg or mean arterial pressure with less than 65 mmHg within the 60-minute period after intubation. The outcome measures were inhospital mortality, as well as intensive care unit and hospital length of stay. RESULTS: The incidence of PIH was 23% (80 of 352 patients). Patients in the PIH group were slightly older and had more comorbid diseases than those in the non-PIH group. PIH patients had a significantly higher mortality rate (54% vs. 30%, p<0.01). PIH was a strong predictor for in-hospital mortality of intubated patients (hazard ratio, 2.3; 95% confidence interval, 1.3 to 3.4). CONCLUSION: Older age, lack of skill, history of hypertension, low albumin and pH, and elevated were risk factors for the occurrence of hypotension after ETI. Patients with PIH show increased risk of in-hospital mortality.

The Effects of Recombinant Synucleins and Insulin-like Growth Factor 1 on Cancer Cell Migration

The synuclein family consists of three distinct genes, alpha-synuclein, beta-synuclein, and gamma-synuclein. The alpha-synuclein and beta-synuclein are predominately expressed in brain and especially alpha-synuclein is related with Parkinson's disease, Alzheimer's disease, and dementia with Lewy bodies. The gamma-synuclein was first identified as breast cancer specific gene 1. It is expressed in the peripheral nervous system and also detected in breast and ovarian cancers. The gamma-synuclein is also known to mediate metastasis of breast and ovarian cancer cells. Insulin-like growth factor 1 (IGF-I) is one of the growth factors that plays an important role in cell proliferation and migration in cancer cells, as well as in normal cells. In this study, we investigated the migrations of SKOV-3, MDAMB-231, and HeLa cells by the recombinant synuclein proteins (alpha-, beta-, and gamma-synucleins) and IGF-I and the molecular mechanism. Furthermore, we investigated the membrane ruffle formation of SKOV-3 cells by recombinant synuclein proteins and IGF-I. As a result, synucleins and IGF-I were found to induce cancer cell migrations. Simultaneous synucleins and IGF-I treatment on the cancer cells induced more migrations than the individual synuclein or IGF-I treatments. The synucleins or IGF-I treatments increased the expressions of membrane-type1 matrix metalloproteinase (MT1-MMP) and cluster of differentiation 44 (CD44). Moreover, simultaneous synucleins and IGF-I treatments further increased the expressions of MT1-MMP and CD44. The synucleins and IGF-I promoted the conformational change of actin filaments, and then this led to the membrane ruffle formation.

Association of Killer Cell Ig-like Receptor (KIR) with an Adaptor Protein Shc

BACKGROUND: Cytotoxic function of killer cells is inhibited by specific recognition of class I MHC molecules on target cells by inhibitory killer Ig-like receptors (KIR) expressed on NK cells and some cytotoxic T cells. The inhibitory effect of KIR is accomplished by recruitment of SH2-containing protein tyrosine phosphatase (SHP) to the phosphotyrosine residues in the cytoplasmic tail. METHODS: By in vitro coprecipitation experiments and transfection analysis, we investigated the association of KIR with an adaptor protein Shc in Jurkat T cells. RESULTS: The cytoplasmic tail of KIR appeared to associate with an adaptor protein Shc in Jurkat T cell lysates. Similar in vitro experiments showed that phosphorylated KIR cytoplasmic tail bound SHP-1 and Shc in Jurkat T cell lysates. The association of KIR with Shc was further confirmed by transfection analysis in 293T cells. Interestingly, however, Shc appeared to be replaced by SHP-2 upon engagement of KIR in 293T cells. CONCLUSION: Our data indicate that KIR associate with an adaptor protein Shc in Jurkat T cells, and suggest that KIR might have an additional role which is mediated by this adaptor protein.

Superantigen and class II MHC molecules

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