Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons

Klaile, Esther; Klassert, TE; Scheffrahn, Inka; Mm, Müller; Heinrich, A; Heyl, KA; Dienemann, H.; Grünewald, Christian; Bals, R; Singer, BB; Slevogt, Hortense

doi:10.1055/s-0035-1544862

Cited by 16 publications

(26 citation statements)

References 19 publications

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“…Furthermore, increased expression of TLR2 and CD14 has been reported on CD8 1 T cells in chronic obstructive pulmonary disease (30,31), and in whole sputum in noneosinophilic asthma, associated with increased sputum endotoxin (32). Thus, upregulation in severe neutrophilic asthma of such innate pathogen receptors on T cells, together with other components of the NF-kB signaling pathway and epithelial upregulation of CEACAM5 (a receptor exploited by airway pathogens, including H. influenzae [18]), constitutes a signature suggestive of bacterial infection driving the inflammation of the airways in these individuals.…”

Section: Discussionmentioning

confidence: 99%

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma

Singhania

Wallington

Smith

et al. 2018

Am J Respir Cell Mol Biol

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Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3 1 T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133 1 PM GeneChips, and results were validated by real-time quantitative PCR. In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma. In severe asthma-with predominantly neutrophilic phenotype-several distinct processes were upregulated, including neutrophilia (TCN1 and MMP9), mucins, and oxidative stress responses. The majority of the disease signature was evident in sputum T cells in severe asthma, where 267 genes were differentially regulated compared with health, highlighting compartmentalization of inflammation. This signature included IL-17-inducible chemokines (CXCL1, CXCL2, CXCL3, IL8, and CSF3) and chemoattractants for neutrophils (IL8, CCL3, and LGALS3), T cells, and monocytes. A protein interaction network in severe asthma highlighted signatures of responses to bacterial infections across tissues (CEACAM5, CD14, and TLR2), including Toll-like receptor signaling. In conclusion, the activation of innate immune pathways in the airways suggests that activated T cells may be driving neutrophilic inflammation and steroid-insensitive IL-17 response in severe asthma.

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Section: Discussionmentioning

confidence: 99%

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma

Singhania

Wallington

Smith

et al. 2018

Am J Respir Cell Mol Biol

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“…We recently demonstrated that CEACAM5 is also expressed in human airways (20). However, despite the fact that M. catarrhalis also binds to CEACAM5 (4,16), the putative hCEACAM5 dependency for epithelial colonization of CEACAM-binding pathogens in airway epithelium has not yet been investigated.…”

mentioning

confidence: 99%

Moraxella catarrhalisinduces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure

Gutbier

Fischer

Doehn

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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In patients with chronic obstructive pulmonary disease (COPD), Moraxella catarrhalis infection of the lower airways is associated with chronic colonization and inflammation during stable disease and acute exacerbations. Chronic smoke exposure induces chronic inflammation and impairs mucociliary clearance, thus contributing to bacterial colonization of the lower airways in COPD patients. The human-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, expressed in human airways, has been shown to contribute to epithelial colonization of CEACAM-binding pathogens. To investigate the impact of CEACAM5 expression on pulmonary M. catarrhalis colonization, we infected mice transgenic for human CEACAM5 (hCEACAM5) and wild type mice intratracheally with M. catarrhalis with or without preceding smoke exposure and analyzed bacterial colonization and local and systemic inflammation. Our results show that airway infection with M. catarrhalis accelerated acute local but not systemic inflammation, albeit independent of hCEACAM5 expression. Long-term smoke exposure alone or prior to M. catarrhalis infection did not contribute to increased local or systemic inflammation. No difference was found in pulmonary clearance of M. catarrhalis in hCEACAM5-transgenic mice compared with wild-type mice. Smoke exposure neither altered time nor extent of persistence of M. catarrhalis in the lungs of both genotypes. In conclusion, M. catarrhalis induced a local acute immune response in murine airways. Neither hCEACAM5 expression nor chronic smoke exposure nor a combination of both was sufficient as prerequisites for the establishment of chronic M. catarrhalis colonization. Our results demonstrate the difficulties in mirroring conditions of chronic airways colonization of M. catarrhalis in a murine model.

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“…Both can bind to CEACAM1 and induce bacterial adherence and internalization in bronchial epithelial cells, triggering the development of AECOPD. A recent study showed that M. catarrhalis and S. pneumonia per se can increase CEACAM1 mRNA level in normal human bronchial epithelial cells [64].…”

Section: Roles Of Ceacam1 In Copdmentioning

confidence: 99%

Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases

Wang

et al. 2015

Cancer Metastasis Rev

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Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a broadly-expressed immunoglobulin-like cell adhesion molecule with a wide range of biological functions to regulate cell signaling. The present article mainly focuses on the role of CEACAM1 as a therapeutic target in lung diseases and discusses the potential of therapeutic strategies targeting CEACAM1. The article overviews the structure and its sub-types, biological function, and potential roles of CEACAM1 in lung diseases. Alterations of CEACAM1 expression and CEACAM1-S/CEACAM1-L ratio promote the growth and metastasis of non-small cell lung carcinoma (NSCLC). Moreover, CEACAM1 mediates bacterial adherence and transcellular transcytosis, resulting in the suppression of immune cell activities and inflammatory responses, which may trigger acute exacerbation of chronic obstructive pulmonary disease (AECOPD). CEACAM1 plays a critical role in the development of NSCLC and AECOPD and can be a diagnostic biomarker and therapeutic target in lung diseases.

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Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons

Cited by 16 publications

References 19 publications

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma

Moraxella catarrhalisinduces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure

Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases

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