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The lung microbiota (or pulmonary microbial community) is a complex variety of microbes found in the lower respiratory tract particularly on the mucus layer and the epithelial surfaces (the lung microbiome refer to their genomes). These microbes include bacteria, yeasts, viruses and bacteriophages. The bacterial part of microbiome has been addressed more deeply. It consists of 9 core genera: ''Prevotella'', ''Sphingomonas'', ''Pseudomonas'', ''Acinetobacter'', ''Fusobacterium'', ''Megasphaera'', ''Veillonella'', ''Staphylococcus'', and ''Streptococcus''. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are ''Moraxella catarrhalis'', ''Haemophilus influenzae'', and ''Streptococcus pneumoniae''. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown. ==Role of the epithelial barrier== The airway epithelium together with alveolar macrophages and dendritic cells play a major role in the initial recognition of bacterial products getting into the lower airways with the air. Since some of these products are potent proinflammatory stimuli it is extremely important for the immune system to distinguish between pathogens and non-pathogenic commensals. This prevents the development of constant inflammation and forms tolerance against harmless microbiota. This process becomes much more intriguing when taking into account that commensals often share their surface molecules with pathogens. Epithelial cells are equipped with very sensitive recognition tools - toll like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) which recognize a broad variety of microbial structural components. After recognition of pathogenic bacteria proinflammatory pathways are activated and cellular components of the adaptive and innate immunity are recruited to the infection site. One key regulator in this process is the NF-κB which translocates from the cytoplasm into the nucleus and activates pro-inflammatory genes in epithelial cells and macrophages. The DNA-binding protein complex recognizes a discrete nucleotide sequence (5’-GGG ACT TTC T-3’) in the upstream region of a variety of response genes. The activation of NF-κB by a number of stimuli: bacterial cell walls or inflammatory cytokines results in its translocation to the nucleus. In contrast, harmless bacteria do not cause the translocation of NF-κB into the nucleus thus preventing the inflammation although they can express the same microbe-associated molecular patterns (MAMPs). One possible mechanism explaining this effect was suggested by Neish showing that non-pathogenic ''S. typhimurium'' PhoPc and ''S. pullorum'' are able to prohibit the ubiquitination of NF-κB inhibitor molecule nuclear factor of NF-κB light polypeptide gene enhancer in B-cells inhibitor alpha (IκB-κ). Another explanation of commensal tolerance of the epithelium refers to the post-translational modification of a protein by the covalent attachment of one or more ubiquitin (Ub) monomers. The inhibition of ubiquitination leads to reduction of inflammation, because only polyubiquitinated (IκB-κ is targeted for degradation by the 26 S proteasome, allowing NF-κB translocation to the nucleus and activation the transcription of effector genes (for example IL-8). Probiotic bacteria such as ''Lactobacilli'' are able to modulate the activity of the Ub-proteasome system via inducing reactive oxygen species (ROS) production in epithelial cells. In mammalian cells, ROS have been shown to serve as critical second messengers in multiple signal transduction pathways in response to proinflammatory cytokines. Bacterially induced ROS causes oxidative inactivation of the catalytic cysteine residue of Ub 12 resulting in incomplete but transient loss of cullin-1 neddylation and consequent effects on NF-κB and β-catenin signaling. Another commensal species, ''B. thetaiotaomicron'', attenuates pro-inflammatory cytokine expression by promoting nuclear export of NF-κB subunit RelA, through a peroxisome proliferator activated receptor γ (PPAR-γ)-dependent pathway. PPAR-γ target transcriptionally active Rel A and induce early nuclear clearance limiting the duration of NF-κB action. The balance between pathogens and commensals is extremely important in the maintenance of homeostasis in the respiratory tract. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Lung microbiome」の詳細全文を読む スポンサード リンク
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