Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis

Waal, Amy M. de; Hiemstra, Pieter S.; Ottenhoff, Tom H. M.; Joosten, Simone A.; Does, Anne M. van der

doi:10.1136/thoraxjnl-2021-217997

Cited by 28 publications

(24 citation statements)

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“…To search for factors secreted by epithelial cells that might contribute to the disease progression, we compiled a custom list of secreted proteins and receptors, including genes expressed by lung epithelial cells during the immune response to mycobacteria( 30 ) or in cross-talk with lung macrophages( 49 ). Filtering the DEGs identified in CK+ cells with this list showed that the advanced lesions expressed higher levels of numerous relevant mediators, e.g.…”

Section: Resultsmentioning

confidence: 99%

Aberrant macrophage activation and failed regeneration of pulmonary epithelium promote tuberculosis progression uniquely in lung tissue

Yabaji,

Lo,

Lata

et al. 2023

Preprint

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Pulmonary TB that develops in immunocompetent adult humans is responsible for approximately 85% of the disease burden and is central for Mtb transmission. Most humans contain Mtb infection within primary granulomatous lesions, but in certain immunocompetent humans, containment fails, leading to hematogenous spread and active pulmonary disease with the formation of necrotic lesions and cavities that enable Mtb transmission via aerosols. To reveal lung-specific microenvironments conducive for Mtb survival and replication despite systemic immunity, we use fluorescence multiplex immunohistochemistry and spatial transcriptomic analyses of heterogenous TB lesions that uniquely form in the lungs of immunocompetent but TB-susceptible B6.Sst1S mice after hematogenous spread from the primary lesion. Initially, these secondary lung lesions manifested local adoptive immunity featuring tertiary lymphoid follicles similar to resistant B6 mice and contained primarily non-replicating bacilli. Following these early events, however, the B6.Sst1S mice uniquely demonstrate expansion of myeloid cell populations with the appearance of alternatively activated macrophages, dissolution of lymphoid follicles, and the accumulation of de-differentiated lung epithelial cells. These processes led to bronchogenic expansion, broncho-occlusion, and necrosuppurative pneumonia closely resembling advanced pulmonary tuberculosis in humans. To determine whether lung parenchymal cells or lung oxygenation were necessary for the pulmonary TB progression, we implanted lung and spleen fragments subcutaneously prior to the infection. The lung implants uniquely displayed the formation of the characteristic organized granulomas with necrosis and Mtb replication that paralleled TB progression in native lungs, demonstrating that the cellular composition of inflamed lung tissue, not oxygenation, is a critical determinant of pulmonary TB progression. Our data demonstrate that deleterious bi-directional interactions of aberrantly activated macrophages with the inflammation-injured lung resident cells determine lung vulnerability to virulent Mtb in immunocompetent hosts. Because these mechanisms enable Mtb transmission among humans via aerosols, they are likely evolutionary conserved and, therefore, represent appealing targets for host-directed TB therapies.

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Section: Resultsmentioning

confidence: 99%

Aberrant macrophage activation and failed regeneration of pulmonary epithelium promote tuberculosis progression uniquely in lung tissue

Yabaji,

Lo,

Lata

et al. 2023

Preprint

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“…Lung homeostasis is the cornerstone of lung health and depends substantially on the pulmonary microenvironment. Communication among the pulmonary epithelium, endotheliocytes, and immune cells dominantly contributes to maintaining the balance of the pulmonary microenvironment. , The dysfunctions of these cells can alter the pulmonary microenvironment, leading to lung inflammation and cancer development. − Various resident cells from the lung can achieve intercellular communication by secreting exosomes carrying a specific high or low expression of miRNA, providing a novel theoretical foundation for the pathogenesis of ALI (Figure ).…”

Section: Role Of Exosomal Mirnas In the Pathogenesis Of Alimentioning

confidence: 99%

Exosomal MicroRNAs: An Emerging Important Regulator in Acute Lung Injury

Lan,

Dong,

Yang

et al. 2023

ACS Omega

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Acute lung injury (ALI) is a clinically life-threatening form of respiratory failure with a mortality of 30%–40%. Acute respiratory distress syndrome is the aggravated form of ALI. Exosomes are extracellular lipid vesicles ubiquitous in human biofluids with a diameter of 30–150 nm. They can serve as carriers to convey their internal cargo, particularly microRNA (miRNA), to the target cells involved in cellular communication. In disease states, the quantities of exosomes and the cargo generated by cells are altered. These exosomes subsequently function as autocrine or paracrine signals to nearby or distant cells, regulating various pathogenic processes. Moreover, exosomal miRNAs from multiple stem cells can provide therapeutic value for ALI by regulating different signaling pathways. In addition, changes in exosomal miRNAs of biofluids can serve as biomarkers for the early diagnosis of ALI. This study aimed to review the role of exosomal miRNAs produced by different sources participating in various pathological processes of ALI and explore their potential significance in the treatment and diagnosis.

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“…The type I alveolar epithelial cell is a large and very thin cell, and its primary function is gas exchange. The type II cell has a cuboidal shape and secretory functions, such as surfactant production [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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

Barros

Almeida

Barros

et al. 2022

JoF

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The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review.

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Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis

Cited by 28 publications

References 121 publications

Aberrant macrophage activation and failed regeneration of pulmonary epithelium promote tuberculosis progression uniquely in lung tissue

Aberrant macrophage activation and failed regeneration of pulmonary epithelium promote tuberculosis progression uniquely in lung tissue

Exosomal MicroRNAs: An Emerging Important Regulator in Acute Lung Injury

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

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