Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes

Jessica Quintin, Sadia Saeed, Joost H.A. Martens, Evangelos J. Giamarellos-Bourboulis, Daniela C. Ifrim, Colin Logie, Liesbeth Jacobs, Trees Jansen, Bart Jan Kullberg, Cisca Wijmenga, Leo A.B. Joosten, Ramnik J. Xavier, Jos W.M. Van Der Meer, Hendrik G. Stunnenberg, Mihai G. Netea

Research output: Contribution to journalArticlepeer-review

842 Citations (Scopus)

Abstract

Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against reinfection. Testing this concept of "trained immunity," we show that mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner. C. albicans and fungal cell wall β-glucans induced functional reprogramming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the β-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. Monocyte training by β-glucans was associated with stable changes in histone trimethylation at H3K4, which suggests the involvement of epigenetic mechanisms in this phenomenon. The functional reprogramming of monocytes, reminiscent of similar NK cell properties, supports the concept of "trained immunity" and may be employed for the design of improved vaccination strategies.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalCell Host and Microbe
Volume12
Issue number2
DOIs
Publication statusPublished - 16 Aug 2012
Externally publishedYes

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