Systemic inflammatory response syndrome triggered by blood-borne pathogens induces prolonged dendritic cell paralysis and immunosuppression

Mitra Ashayeripanah; Javier Vega-Ramos; Daniel Fernandez-Ruiz; Shirin Valikhani; Aaron TL Lun; Jason T White; Louise J Young; Atefeh Yaftiyan; Yifan Zhan; Linda Wakim; Irina Caminschi; Mireille H Lahoud; Andrew M Lew; Ken Shortman; Gordon K Smyth; William R Heath; Justine D Mintern; Antoine Roquilly; Jose A Villadangos

Journal article

Systemic inflammatory response syndrome triggered by blood-borne pathogens induces prolonged dendritic cell paralysis and immunosuppression

Mitra Ashayeripanah, Javier Vega-Ramos, Daniel Fernandez-Ruiz, Shirin Valikhani, Aaron TL Lun, Jason T White, Louise J Young, Atefeh Yaftiyan, Yifan Zhan, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Andrew M Lew, Ken Shortman, Gordon K Smyth, William R Heath, Justine D Mintern, Antoine Roquilly, Jose A Villadangos

Cell Reports | Elsevier | Published : 2024

DOI: 10.1016/j.celrep.2024.113754

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Abstract

Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3–4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone..

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University of Melbourne Researchers

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Fellowships 1154970 (G.K.S.) , 1058193 (J.A.V.) , and 1154502 (J.A.V.) , program grants 1016629 (W.R.H., K.S., and J.A.V.) and 1113293 (W.R.H. and J.A.V.) , and project grant 1163090 (A.R. and J.A.V.) ; the Societe Francaise d'Anesthesie et de Reanimation (A.R.) ; the Fondation des Gueules Cassees (A.R.) ; Agence National pour le Recherche (A.R.) ; and the Fundacion Pedro i Pons (J.V.-R.) . We thank Prof Axel Kallies (University of Melbourne) for the TGFbR-II<SUP>fl/fl</SUP> CD11c<SUP>cre </SUP>mice.