Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections

Barros, Bianca Carla Silva Campitelli; Almeida, Bruna Rocha; Barros, Debora Tereza Lucas; Toledo, Marcos S.; Suzuki, Érika

doi:10.3390/jof8060548

Cited by 6 publications

(4 citation statements)

References 97 publications

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“…Pulmonary epithelial cells play a central role in orchestrating the host defense against pulmonary pathogens by secreting proinflammatory cytokines and chemokines that attract and activate professional phagocytes that kill the invading microorganisms ( 33 – 36 ). To compare the inflammatory responses of A549 and HSAE cells to A. fumigatus , we infected them for 24 h with conidia of two different strains of A. fumigatus and measured the levels of eight cytokines and chemokines using a Luminex multiplex array.…”

Section: Resultsmentioning

confidence: 99%

Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells

Liu

Lin

Phan

et al. 2023

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During the initiation of invasive aspergillosis, inhaled Aspergillus fumigatus conidia are deposited on the epithelial cells lining the bronchi, terminal bronchioles, and alveoli. While the interactions of A. fumigatus with bronchial and type II alveolar cell lines have been investigated in vitro , little is known about the interactions of this fungus with terminal bronchiolar epithelial cells. Using the HSAEC1-KT human small airway epithelial (HSAE) cell line, we developed an in vitro model to study the interaction of two strains of A. fumigatus with these cells. We then compared the interactions of A. fumigatus with the A549 type II alveolar epithelial cell line and the HSAE cell line. We found that A. fumigatus conidia were poorly endocytosed by A549 cells, but avidly endocytosed by HSAE cells. A. fumigatus germlings invaded both cell types by induced endocytosis, but not by active penetration. A549 cell endocytosis of A. fumigatus was independent of fungal viability, more dependent on host microfilaments than microtubules, and induced by A. fumigatus CalA interacting with host cell integrin α5β1. By contrast, HSAE cell endocytosis required fungal viability, was more dependent on microtubules than microfilaments, and did not require CalA or integrin α5β1. HSAE cells were more susceptible than A549 cells to damage caused by direct contact with killed A. fumigatus germlings and by secreted fungal products. In response to A. fumigatus infection, A549 cells secreted a broader profile of cytokines and chemokines than HSAE cells. Taken together, these results demonstrate that studies of HSAE cells provide complementary data to A549 cells and thus represent a useful model for probing the interactions of A. fumigatus with bronchiolar epithelial cells in vitro . IMPORTANCE During the initiation of invasive aspergillosis, Aspergillus fumigatus interacts with the epithelial cells that line the airways and alveoli. Previous studies of A. fumigatus -epithelial cell interactions in vitro used either large airway epithelial cell lines or the A549 type II alveolar epithelial cell line; the interactions of fungi with terminal bronchiolar epithelial cells were not investigated. Using the TERT-immortalized human small airway epithelial HSAEC1-KT (HSAE) cell line, we developed an in vitro model of the interactions of A. fumigatus with bronchiolar epithelial cells. We discovered that A. fumigatus invades and damages A549 and HSAE cell lines by distinct mechanisms. Also, the proinflammatory responses of the cell lines to A. fumigatus are different. These results provide insight into how A. fumigatus interacts with different types of epithelial cells during invasive aspergillosis and demonstrate that HSAE cells are useful in vitro model for investigating the interactions of this fungus with bronchiolar epithelial cells.

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Section: Resultsmentioning

confidence: 99%

Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells

Liu

Lin

Phan

et al. 2023

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“…The goal of our research group has been to understand the responses of human lung epithelial cells after interaction with the human respiratory pathogenic fungi Paracoccidioides and Histoplasma capsulatum [ 4 , 15 , 16 , 23 , 24 , 26 , 36 , 37 , 38 , 39 ]. We have observed over the years that the integrin family receptors of lung epithelial cells participate in fungal adhesion and cytokine secretion during interaction with Paracoccidioides yeasts [ 15 , 16 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Besides forming a physical barrier in the body, respiratory epithelial cells have various receptors that constantly monitor the inhaled air to detect pathogens. As a result, epithelial cells may release chemical mediators, such as cytokines and chemokines, that promote the recruitment and activation of immune cells at the site of infection [ 4 ]. Pathogens, in turn, may interact with the host cell receptors and consequently manipulate cell signaling pathways to subvert host defenses, survive, and establish an infection in the host [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Paracoccidioides brasiliensis Induces α3 Integrin Lysosomal Degradation in Lung Epithelial Cells

Almeida,

Barros,

Barros

et al. 2023

JoF

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Studies on the pathogen–host interaction are crucial for the understanding of the mechanisms involved in the establishment, maintenance, and spread of infection. In recent years, our research group has observed that the P. brasiliensis species interact with integrin family receptors and increase the expression of α3 integrin in lung epithelial cells within 5 h of infection. Interestingly, α3 integrin levels were reduced by approximately 99% after 24 h of infection with P. brasiliensis compared to non-infected cells. In this work, we show that, during infection with this fungus, α3 integrin is increased in the late endosomes of A549 lung epithelial cells. We also observed that the inhibitor of the lysosomal activity bafilomycin A1 was able to inhibit the decrease in α3 integrin levels. In addition, the silencing of the charged multivesicular body protein 3 (CHMP3) inhibited the reduction in α3 integrin levels induced by P. brasiliensis in A549 cells. Thus, together, these results indicate that this fungus induces the degradation of α3 integrin in A549 lung epithelial cells by hijacking the host cell endolysosomal pathway.

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“…Airway epithelial cells comprise the physical barrier between the respiratory system and the external environment, which is at the forefront of defense against harmful inhaled substances and plays a crucial role in inflammatory responses, immune responses, and airway repair. 17 The destruction of the airway epithelial barrier is a major issue in the pathogenesis of asthma. 18 Injury and abscission of airway epithelium were found in bronchoscopic biopsy tissues of patients with moderate to severe asthma, 19 , 20 which may be a result of excessive apoptosis of airway epithelial cells.…”

Section: Apoptosis In Asthmamentioning

confidence: 99%

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

Lü¹,

Zhou²,

Wang³

et al. 2023

JIR

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Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.

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Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections

Cited by 6 publications

References 97 publications

Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells

Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells

Paracoccidioides brasiliensis Induces α3 Integrin Lysosomal Degradation in Lung Epithelial Cells

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

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