Immune signature of acute pharyngitis in a Streptococcus pyogenes human challenge trial

Jeremy Anderson, Samira Imran, Hannah R. Frost, Kristy I. Azzopardi, Sedigheh Jalali, Boris Novakovic, Joshua Osowicki (), Andrew C. Steer (), Paul V. Licciardi () and Daniel G. Pellicci ()
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Jeremy Anderson: Murdoch Children’s Research Institute
Samira Imran: Murdoch Children’s Research Institute
Hannah R. Frost: Murdoch Children’s Research Institute
Kristy I. Azzopardi: Murdoch Children’s Research Institute
Sedigheh Jalali: Murdoch Children’s Research Institute
Boris Novakovic: Murdoch Children’s Research Institute
Joshua Osowicki: Murdoch Children’s Research Institute
Andrew C. Steer: Murdoch Children’s Research Institute
Paul V. Licciardi: Murdoch Children’s Research Institute
Daniel G. Pellicci: Murdoch Children’s Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Streptococcus pyogenes causes at least 750 million infections and more than 500,000 deaths each year. No vaccine is currently available for S. pyogenes and the use of human challenge models offer unique and exciting opportunities to interrogate the immune response to infectious diseases. Here, we use high-dimensional flow cytometric analysis and multiplex cytokine and chemokine assays to study serial blood and saliva samples collected during the early immune response in human participants following challenge with S. pyogenes. We find an immune signature of experimental human pharyngitis characterised by: 1) elevation of serum IL-1Ra, IL-6, IFN-γ, IP-10 and IL-18; 2) increases in peripheral blood innate dendritic cell and monocyte populations; 3) reduced circulation of B cells and CD4+ T cell subsets (Th1, Th17, Treg, TFH) during the acute phase; and 4) activation of unconventional T cell subsets, γδTCR + Vδ2+ T cells and MAIT cells. These findings demonstrate that S. pyogenes infection generates a robust early immune response, which may be important for host protection. Together, these data will help advance research to establish correlates of immune protection and focus the evaluation of vaccines.

Date: 2022
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DOI: 10.1038/s41467-022-28335-3

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