Telomerase RNA component knockout exacerbates <i>Staphylococcus aureus</i> pneumonia by extensive inflammation and dysfunction of T cells.

Abstract

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 <i>Staphylococcus aureus (S. aureus</i>) in <i>Terc</i> knockout (<i>Terc</i>^ko/ko) mice compared to both young and old infected counterparts. The exacerbated infection in <i>Terc</i>^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 <i>Terc</i>^ko/ko, inflammation, and impaired T cell functionality. <i>Terc</i> 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 <i>S. aureus</i>. 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.