Fisher-Pearson, N. | Search bioRxiv

bioRxiv2026

Gut archaea drive human MAIT cell responses

Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing microbiomes from UK, Zambian, Kenyan and Ugandan donors, we found strong correlations between archaeal riboflavin biosynthesis and circulating MAIT cell frequency and activation. Stool 5-OP-RU levels correlated with archaeal abundance. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii, produced 5-OP-RU and strongly activated MAIT cells without inflammation. We demonstrate a critical role for archaea in shaping human immunity, with implications for microbiome-mediated regulation of health.

immunology↗

bioRxiv2021

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH. One Sentence SummaryAdaptive immune responses to SARS-CoV-2 in the setting of HIV infection

immunology↗