Nontypeable Haemophilus influenzae (NTHi) directly interfere with the regulation of E-cadherin in lung epithelial cells

Kaufhold, Inga; Osbahr, Sünja; Shima, Kensuke; Marwitz, Sebastian; Rohmann, K; Drömann, Daniel; Goldmann, Torsten; Dalhoff, K; Rupp, Jan

doi:10.1016/j.micinf.2017.07.002

Cited by 10 publications

(7 citation statements)

References 28 publications

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“…Infections with NTHi have also been shown to reduce cellular levels of E-cadherin, a protein required for tight junction formation and epithelial cell integrity in human cells ( 231 ). Considering that perturbations in the epithelial cell barrier caused by the loss of E-cadherin is a common symptom of COPD, NTHi-mediated exacerbations likely contribute to this step of COPD pathogenesis.…”

Section: Colonization and Adaptation Of Nthi In The Lower Airways Of mentioning

confidence: 99%

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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Section: Colonization and Adaptation Of Nthi In The Lower Airways Of mentioning

confidence: 99%

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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“…RSV infection was shown to downregulate the expression of claudin-1 and occludin in a mouse model, inhibiting barrier function as mediated by tight junctions (198). Infection with H. influenzae was also demonstrated to downregulate host transcription of e-cadherin through inhibition of FGF2, mTOR, and Slug (199). IAV infection was also shown to damage respiratory epithelial cell barrier integrity by downregulating the expression of tight junction protein claudin-4 (200).…”

Section: Modulation Of Respiratory Epithelial Barrier Dynamicsmentioning

confidence: 99%

“…Compounds causing an upregulation in gene expression or assembly of junction proteins on respiratory epithelial cells could be promising tolerance-augmenting therapeutics for use during diverse viral primary infections. Many bacterial and fungal pathogens of the lung, including S. pneumoniae, S. aureus, Candida albicans, and P. aeruginosa, employ adhesion junction components, specifically E-cadherin, as an adherence or entry receptor for invasion and colonization (199). The severity of phenotypes observed due to the alpha-toxin protein of S. aureus has also been shown to be modulated by the abundance of functional adherens junctions (204).…”

Section: Modulation Of Respiratory Epithelial Barrier Dynamicsmentioning

confidence: 99%

Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System

et al. 2018

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Much research on infectious diseases focuses on clearing the pathogen through the use of antimicrobial drugs, the immune response, or a combination of both. Rapid clearance of pathogens allows for a quick return to a healthy state and increased survival. Pathogen-targeted approaches to combating infection have inherent limitations, including their pathogen-specific nature, the potential for antimicrobial resistance, and poor vaccine efficacy, among others. Another way to survive an infection is to tolerate the alterations to homeostasis that occur during a disease state through a process called host tolerance or resilience, which is independent from pathogen burden. Alterations in homeostasis during infection are numerous and include tissue damage, increased inflammation, metabolic changes, temperature changes, and changes in respiration. Given its importance and sensitivity, the lung is a good system for understanding host tolerance to infectious disease. Pneumonia is the leading cause of death for children under five worldwide. One reason for this is because when the pulmonary system is altered dramatically it greatly impacts the overall health and survival of a patient. Targeting host pathways involved in maintenance of pulmonary host tolerance during infection could provide an alternative therapeutic avenue that may be broadly applicable across a variety of pathologies. In this review, we will summarize recent findings on tolerance to host lung infection. We will focus on the involvement of innate immune responses in tolerance and how an initial viral lung infection may alter tolerance mechanisms in leukocytic, epithelial, and endothelial compartments to a subsequent bacterial infection. By understanding tolerance mechanisms in the lung we can better address treatment options for deadly pulmonary infections.

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“…The airway epithelial barrier is the first line of protection against inhaled particulates, antigens and pathogens [ 57 , 58 ], but in allergic diseases such as asthma there is a loss of differentiation, reduced junctional integrity and impaired innate defence [ 59 ]. NTHi infection reduces the expression of the tight-junction protein E-cadherin in vitro [ 60 ], suggesting that NTHi infection may reduce epithelial barrier integrity. Moreover, NLRP3 activation via NF-κB and IκB kinase can reduce tight-junction integrity [ 61 ].…”

Section: Pathogenesis Of Nthi Infection In Airways Diseasementioning

confidence: 99%

Non-typeableHaemophilus influenzaeairways infection: the next treatable trait in asthma?

et al. 2022

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Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.

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Nontypeable Haemophilus influenzae (NTHi) directly interfere with the regulation of E-cadherin in lung epithelial cells

Cited by 10 publications

References 28 publications

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

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

Surviving Deadly Lung Infections: Innate Host Tolerance Mechanisms in the Pulmonary System

Non-typeableHaemophilus influenzaeairways infection: the next treatable trait in asthma?

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