Open AccessRapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins
Author(s) -
Thuan Nguyen,
Gordon Y. C. Cheung,
Kevin M. Rigby,
Olena Kamenyeva,
Juraj Kabát,
Daniel E. Sturdevant,
Amer E. Villaruz,
Ryan Liu,
Pipat Piewngam,
Adeline R. Porter,
Saba Firdous,
Janice Chiou,
Matthew D. Park,
Rachelle L. Hunt,
Fawaz M F Almufarriji,
Vee Y. Tan,
Titus K. Asiamah,
Joshua W. McCausland,
Emilie L. Fisher,
Anthony J. Yeh,
Justin S. Bae,
Scott D. Kobayashi,
Ji Ming Wang,
Daniel L. Barber,
Frank R. DeLeo,
Michael Otto
Publication year - 2021
Publication title -
nature microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.305
H-Index - 79
ISSN - 2058-5276
DOI - 10.1038/s41564-021-01012-9
Subject(s) - immune system , effector , biology , microbiology and biotechnology , pathogen , staphylococcus aureus , innate immune system , pathogen associated molecular pattern , immunology , bacteria , pattern recognition receptor , genetics
Swift recruitment of phagocytic leucocytes is critical in preventing infection when bacteria breach through the protective layers of the skin. According to canonical models, this occurs via an indirect process that is initiated by contact of bacteria with resident skin cells and which is independent of the pathogenic potential of the invader. Here we describe a more rapid mechanism of leucocyte recruitment to the site of intrusion of the important skin pathogen Staphylococcus aureus that is based on direct recognition of specific bacterial toxins, the phenol-soluble modulins (PSMs), by circulating leucocytes. We used a combination of intravital imaging, ear infection and skin abscess models, and in vitro gene expression studies to demonstrate that this early recruitment was dependent on the transcription factor EGR1 and contributed to the prevention of infection. Our findings refine the classical notion of the non-specific and resident cell-dependent character of the innate immune response to bacterial infection by demonstrating a pathogen-specific high-alert mechanism involving direct recruitment of immune effector cells by secreted bacterial products.