O-Acetylation of Peptidoglycan Limits Helper T Cell Priming and Permits Staphylococcus aureus Reinfection

Publication date: Available online 21 September 2017
Source:Cell Host & Microbe
Author(s): Marisel Sanchez, Stacey L. Kolar, Sabrina Müller, Christopher N. Reyes, Andrea J. Wolf, Chihiro Ogawa, Rajat Singhania, Daniel D. De Carvalho, Moshe Arditi, David M. Underhill, Gislâine A. Martins, George Y. Liu
Humans do not usually develop effective immunity to Staphylococcus aureus reinfection. Using a murine model that mimics human infection, we show that lack of protective immunity to S. aureus systemic reinfection is associated with robust interleukin-10 (IL-10) production and impaired protective Th17 responses. In dendritic cell co-culture assays, priming with S. aureus promotes robust T cell proliferation, but limits Th cells polarization and production of IL-1β and other cytokines important for Th1 and Th17 differentiation. We show that O-acetylation of peptidoglycan, a mechanism utilized by S. aureus to block bacterial cell wall breakdown, limits the induction of pro-inflammatory signals required for optimal Th17 polarization. IL-10 deficiency in mice restores protective immunity to S. aureus infection, and adjuvancy with a staphylococcal peptidoglycan O-acetyltransferase mutant reduces IL-10, increases IL-1β, and promotes development of IL-17-dependent, Th cell-transferable protective immunity. Overall, our study suggests a mechanism whereby S. aureus modulates cytokines critical for induction of protective Th17 immunity.

Graphical abstract

Teaser

Humans do not develop robust protective immunity to S. aureus infection. Sanchez et al. show that mice, like humans, do not develop a protective Th17 response after bloodstream S. aureus infection. S. aureus, via modification of cell wall peptidoglycan, limits priming of Th17 cells and blocks development of protective immunity.


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