Distinct commensal bacteria in human nasopharyngeal lymphoid tissue associated with localized immunological memory

The nasopharynx (NP) serves as a primary site for localized immune responses that restrict the spread of SARS-CoV-2 to the lower respiratory tract. The microbiome is increasingly recognized as a key modulator of antiviral immunity but whether it shapes immune responses in upper airway remains uncharacterized. Detailed microbial profiles revealed that <i>S</i>. <i>aureus</i> complex abundance was the primary discriminating factor of microbial community in the NP and the enhanced abundance of <i>S</i>. <i>aureus</i> complex correlated with higher frequencies of CD4⁺, CD8⁺ tissue-resident memory T (T_RM), and B_RM cells. The abundance of <i>S</i>. <i>aureus</i> complex was closely associated with distinct metabolic pathways, particularly those involved in nitrogen metabolism (e.g., arginine, ornithine, and proline interconversion) and the mevalonate pathway for carotenoid biosynthesis. These findings suggest that <i>S</i>. <i>aureus</i> complex may foster unique metabolic dynamics in the NP in enhancing the tissue-residency of memory cells and localized immune responses in upper airway.