Emerging Microbes & Infections最新文献

Older adults remain highly vulnerable to severe SARS-CoV-2 outcomes despite multiple vaccinations, yet age-associated differences in immune responses to updated COVID-19 booster vaccines remain incompletely characterized. Here, we administered an XBB.1.5 trivalent recombinant protein booster (WSK-V102C) to 22 individuals (<38 years) and 20 individuals (≥73 years), all of whom had previously received 2-3 doses of inactivated COVID-19 vaccines. Neutralizing antibody responses against multiple SARS-CoV-2 variants were quantified and compared between age groups. Meanwhile, single-cell RNA sequencing was also performed on peripheral blood mononuclear cells (PBMCs) collected at baseline and 28 days post-vaccination to profile age-associated immune features following boosting. Following booster immunization, both age groups achieved significantly elevated antibody titers against all tested strains. Nevertheless, the magnitude of antibody fold increase was consistently lower in elderly individuals than in younger adults. Single-cell analyses revealed age-associated differences in post-vaccination immune organization. In elderly individuals, B-cell state transitions were characterized by transcriptional signatures consistent with memory B cell-to-plasmablast differentiation, whereas younger individuals predominantly exhibited transitions from naïve B cells. CD4+ T cells from elderly individuals displayed altered transcriptional trajectories and reduced T-cell receptor diversity relative to younger adults. In contrast, younger individuals showed coordinated B- and T-cell-associated transcriptional programs, including enrichment of transcription factors such as KLF7, CEBPB, CEBPD, and MAFB. Collectively, our study describes age-associated differences in immune coordination and cellular response patterns following XBB.1.5 booster vaccination. Further longitudinal and functional studies will be required to clarify the mechanistic basis and clinical implications of these observations.

Streptococcus suis serotype 2 (SS2), a significant zoonotic pathogen, initiates systemic infection by breaching the respiratory epithelial barrier. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly implicated in the pathogenesis of various infectious diseases, yet its role in SS2-induced epithelial barrier dysfunction remains unknown. Here, we demonstrate SS2 infection sensitizes airway epithelial cells to ferroptosis, leading to the accumulation of lipid peroxides, upregulation of the transcriptional repressor Snail1, and subsequent downregulation of intercellular junction proteins. This cascade compromises epithelial integrity and promotes bacterial translocation. Mechanistically, we found SS2 overwhelms the cellular redox defense system and identified bacterial eukaryotic-like serine/threonine kinase 1 (Stk1) as the key mediator of this process. Stk1 directly interacts with host protein Keap1, which stabilizes the Keap1-Nrf2 complex. This stabilization enhances the ubiquitination and subsequent proteasomal degradation of Nrf2, the master regulator of antioxidant response, thereby crippling cell's ability to neutralize lipid peroxides. In summary, this study unveils a novel virulence mechanism wherein SS2 effector Stk1 promotes Nrf2 degradation to trigger ferroptosis, ultimately leading to the disruption of respiratory epithelial barrier. These findings suggest that inhibiting ferroptosis could represent a promising therapeutic strategy for clinical prevention and treatment of SS2 infections.