Aging is associated with a gradual loss of lung function due to increased cellular senescence, decreased regenerative capacity, and impaired innate host defense. One important aspect of innate airway epithelial host defense to nonmicrobial triggers is the secretion of alarmins such as IL-33 and activation of type 2 inflammation, which were previously found to depend on activation of the NADPH oxidase (NOX) homolog DUOX1, and redox-dependent signaling pathways that promote alarmin secretion. Here, we demonstrate that normal aging of C57BL/6J mice resulted in markedly decreased lung innate epithelial type 2 responses to exogenous triggers such as the airborne allergen , which was associated with marked downregulation of DUOX1, as well as DUOX1-mediated redox-dependent signaling. DUOX1 deficiency was also found to accelerate age-related airspace enlargement and decline in lung function but did not consistently affect other features of lung aging such as senescence-associated inflammation. Intriguingly, observations of age-related DUOX1 downregulation and enhanced airspace enlargement due to DUOX1 deficiency in C57BL/6J mice, which lack a functional mitochondrial nicotinamide nucleotide transhydrogenase (NNT), were much less dramatic in C57BL/6NJ mice with normal NNT function, although the latter mice also displayed impaired innate epithelial injury responses with advancing age. Overall, our findings indicate a marked aging-dependent decline in (DUOX1-dependent) innate airway injury responses to external nonmicrobial triggers, but the impact of aging on DUOX1 downregulation and its significance for age-related senile emphysema development was variable between different C57BL6 substrains, possibly related to metabolic alterations due to differences in NNT function.
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http://dx.doi.org/10.1152/ajplung.00021.2021 | DOI Listing |
Microb Pathog
December 2024
Department of Neonatology, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong Province, 518107, China. Electronic address:
Background: Streptococcus agalactiae poses a significant threat to neonatal health, causing morbidity and mortality when transmitted from the maternal vagina to the newborn's respiratory tract. Among its various strains, serotype III is predominant in severe neonatal infections in Asia. However, the mechanisms of pathogenesis and host responses underlying serotype-specific disease outcomes remain poorly understood.
View Article and Find Full Text PDFCell
December 2024
Department of Immunology, University of Toronto, Toronto, ON, Canada. Electronic address:
The underlying mechanisms used by the intestinal microbiota to shape disease outcomes of the host are poorly understood. Here, we show that the gut commensal protozoan, Tritrichomonas musculis (T.mu), remotely shapes the lung immune landscape to facilitate perivascular shielding of the airways by eosinophils.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
December 2024
Keio University School of Medicine, Division of Pulmonary Medicine, Department of Medicine, Tokyo, Japan.
Airway epithelial cells (AECs) play an essential role in the immune response during bacterial pneumonia. Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early (SP) infection. However, its function remains largely unexplored.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria.
Introduction: Airway epithelial cells play a central role in the innate immune response to invading bacteria, yet adequate human infection models are lacking.
Methods: We utilized mucociliary-differentiated human airway organoids with direct access to the apical side of epithelial cells to model the initial phase of respiratory tract infection.
Results: Immunofluorescence of infected organoids revealed that invades the epithelial barrier and subsequently proliferates within the epithelial space.
J Clin Med
December 2024
Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, 08907 Barcelona, Spain.
In patients with aspirin-exacerbated respiratory disease (AERD), there is disparate regulation of prostaglandin E2 (PGE) and prostaglandin D (PGD). Both prostanoids are synthesised by cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). However, while the basal synthesis of PGE tends to decrease, that of PGD increases in patients with AERD.
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