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Telomerase RNA component knockout exacerbates Staphylococcus aureus pneumonia by extensive inflammation and dysfunction of T cells
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Journal Article
Telomerase RNA component knockout exacerbates Staphylococcus aureus pneumonia by extensive inflammation and dysfunction of T cells
2024
Overview
The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation. Our study unveils heightened susceptibility to pneumonia caused by Staphylococcus aureus (S. aureus ) in Terc knockout ( Terc ko/ko ) mice compared to both young and old infected counterparts. The exacerbated infection in Terc ko/ko mice correlates with heightened inflammation, manifested by elevated interleukin-1β (IL-1β) levels and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome within the lung. Employing mRNA sequencing methods alongside in vitro analysis of alveolar macrophages (AMs) and T cells, our study elucidates a compelling correlation between Terc ko/ko , inflammation, and impaired T cell functionality. Terc deletion results in compromised T cell function, characterized by dysregulation of the T cell receptor and absence of CD247, potentially compromising the host’s capacity to mount an effective immune response against S. aureus . This investigation provides insights into the intricate mechanisms governing increased vulnerability to severe pneumonia in the context of Terc deficiency, which might also contribute to aging-related pathologies, while also highlighting the influence of Terc on T cell function.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Aging
/ Alveoli
/ Animals
/ B cells
/ Interleukin-1beta - genetics
/ Interleukin-1beta - metabolism
/ Kinases
/ Lungs
/ Macrophages, Alveolar - immunology
/ Mice
/ Microbiology and Infectious Disease
/ mRNA
/ NLR Family, Pyrin Domain-Containing 3 Protein - genetics
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Pneumonia, Staphylococcal - genetics
/ Pneumonia, Staphylococcal - immunology
/ Pneumonia, Staphylococcal - microbiology
/ RNA
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus infections
/ T cells
/ Terc
