Fungal chitin induces trained immunity in human monocytes during cross-talk with Saccharomyces cerevisiae

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Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk with Saccharomyces cerevisiae

Noemi Tocci1_{, Lisa Rizzetto}1¶_{, Daniela C. Ifrim}2_,_{Shih-Chin Cheng}2_{, Jessica Quintin}2#_{, Carlotta De}

Filippo1_{, Tobias Weil}1_{, Marcello S. Lenucci}3_{, Manuel A. S. Santos}4_{, Mihai G. Netea}2*_{, Duccio}

Cavalieri1,5*

1_{Research and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all’Adige (TN),}

Italy

2_{Radboud University Medical Center, Department of Internal Medicine, Division of Experimental}

Internal Medicine, 6500HB Nijmegen, The Netherlands

3_{Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali (Di.S.Te.B.A.), Università del}

Salento, via Prov.le Lecce-Monteroni, 73100 Lecce, Italy

4_{Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro, Portugal}

5_{Department of Neuroscience, Psychology, Drug Research and Child Health (Neurofarba),}

University of Florence, 50139 Firenze, Italy

#_{Current Address: Immunology of Fungal Infections group, Mycology Department, Institut Pasteur,}

75724 Paris Cedex 15, France Objectives:

Candida albicans, a common colonizer of the human mucosa, is able to train innate immune cells in a process mediated by the β-glucans present in the cell wall1_{. Saccaromyces cerevisiae is another}

constant but harmful colonizer of humans and recently it has been demonstrated to be even more abundant than C. albicans2_{. The aim of this study was to investigate the in vitro training properties}

of S.cerevisiae on innate immune cells and the relation occurring between the cell wall composition and the observed effect.

Methods:

S. cerevisiae isolates from diverse ecological niches have been tested for their ability to induce trained immunity on human monocytes. The cell wall sugar composition of the S. cerevisiae strains have been investigated through ion-exchange chromatography. Glucan, mannan and chitin have been extracted from the yeast cell wall and tested independently for their capabilities to induce immune response.

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The S. cerevisiae clinical isolates were able to strongly enhance pro-inflammatory cytokine production when monocytes were exposed to a secondary bacterial or fungal stimulus. Among cell wall components a higher content of chitin was detected in S. cerevisiae clinical isolates. Chitin was able alone to induce a potent immune response in terms of IL-6 and TNFα and to enhance the phagocytic killing by monocytes.

Conclusions:

The study gives novel prespective on how S.cerevisiae, a passenger microorganism present from centuries in our foods, could help priming organismal protection against pathogens. The chitin-induced training immunity suggests the importance of yeast cell wall modulation in protecting from dysbiosis.

References:

1. Ifrim DC, Joosten LAB, Kullberg B-J, Jacobs L, Jansen T, Williams DL, et al. Candida albicans primes TLR cytokine responses through a Dectin-1/Raf-1-mediated pathway. J Immunol Baltim Md 1950. 2013;190: 4129–4135. doi:10.4049/jimmunol.1202611

2. Angebault C, Djossou F, Abélanet S, Permal E, Ben Soltana M, Diancourt L, et al. Candida albicans is not always the preferential yeast colonizing humans: a study in Wayampi Amerindians. J Infect Dis. 2013;208: 1705–1716. doi:10.1093/infdis/jit389