The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

Hussell, Tracy; Liu, Sylvia; Jagger, Christopher; Morgan, D. O.; Brand, Stephan

doi:10.1183/16000617.0032-2018

Cited by 16 publications

(16 citation statements)

References 73 publications

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“…Furthermore, the expression patterns of CD69, CD49a and CD103 might also translate to different localization of distinct trNK cell subsets in lung. For example, E-cadherin, the ligand for CD103, and collagen IV, the ligand for CD49a, are expressed by epithelial cells lining the alveolar structures in the lung, and the underlying basement membrane 33 , respectively. Human CD103 + CD8 + T RM cells have previously been shown to be located within the lung epithelium 14 , suggesting that expression of CD103 is indeed indicative of an intraepithelial localization within the lung.…”

Section: Discussionmentioning

confidence: 99%

Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells

et al. 2019

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Human lung tissue-resident NK cells (trNK cells) are likely to play an important role in host responses towards viral infections, inflammatory conditions and cancer. However, detailed insights into these cells are still largely lacking. Here we show, using RNA sequencing and flow cytometry-based analyses, that subsets of human lung CD69 + CD16 − NK cells display hallmarks of tissue-residency, including high expression of CD49a, CD103, and ZNF683, and reduced expression of SELL, S1PR5, and KLF2/3. CD49a + CD16 − NK cells are functionally competent, and produce IFN-γ, TNF, MIP-1β, and GM-CSF. After stimulation with IL-15, they upregulate perforin, granzyme B, and Ki67 to a similar degree as CD49a − CD16 − NK cells. Comparing datasets from trNK cells in human lung and bone marrow with tissue-resident memory CD8 + T cells identifies core genes co-regulated either by tissue-residency, cell-type or location. Together, our data indicate that human lung trNK cells have distinct features, likely regulating their function in barrier immunity.

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Section: Discussionmentioning

confidence: 99%

Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells

et al. 2019

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“…Several studies have documented that COPD progression from stable state to an exacerbation could induce microbiota shift in the lower airway (bronchioles), sputum, and throat ( 151 , 190 – 196 ). Alteration in the microbiome complexity or richness is associated with the inflammatory process and changes in ECM protein expression in the lung, as observed in COPD ( 185 , 197 ). Declined diversity in the lung microbiome has been reported to be related to disease severity, inflammation and decreased lung functions in COPD.…”

Section: Acute Exacerbations Of Copd (Aecopd) and Association With MImentioning

confidence: 94%

The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae

Jalalvand

Thegerström

et al. 2018

Front. Immunol.

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Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.

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“…Likewise, during lung infections by Streptococcus, Pseudomonas , and Moraxella , laminin, collagen I, V, and VI are involved in adhesion and invasion ( 111 ). Since the levels of ECM proteins (fibronectin/fibrinogen/collagen/laminins/fibulin-1c) are altered in patients with COPD, relationship between smoking, pathogenic microbes and ECM need to be explored ( 107 , 112 – 114 ).…”

Section: Lung Microbiome and Copdmentioning

confidence: 99%

Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases

et al. 2020

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Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis, and lung cancer, pose a huge socioeconomic burden on society and are one of the leading causes of death worldwide. In the past, culture-dependent techniques could not detect bacteria in the lungs, therefore the lungs were considered a sterile environment. However, the development of culture-independent techniques, particularly 16S rRNA sequencing, allowed for the detection of commensal microbes in the lung and with further investigation, their roles in disease have since emerged. In healthy individuals, the predominant commensal microbes are of phylum Firmicutes and Bacteroidetes, including those of the genera Veillonella and Prevotella. In contrast, pathogenic microbes (Haemophilus, Streptococcus, Klebsiella, Pseudomonas) are often associated with lung diseases. There is growing evidence that microbial metabolites, structural components, and toxins from pathogenic and opportunistic bacteria have the capacity to stimulate both innate and adaptive immune responses, and therefore can contribute to the pathogenesis of lung diseases. Here we review the multiple mechanisms that are altered by pathogenic microbiomes in asthma, COPD, lung cancer, and lung fibrosis. Furthermore, we focus on the recent exciting advancements in therapies that can be used to restore altered microbiomes in the lungs.

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The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

Cited by 16 publications

References 73 publications

Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells

Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells

The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae

Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases

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