Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus aureus for virulence

Masafumi Nakayama, Kenji Kurokawa, Kyohei Nakamura, Bok Luel Lee, Kazuhisa Sekimizu, Hiromi Kubagawa, Keiichi Hiramatsu, Hideo Yagita, Ko Okumura, Toshiyuki Takai, David M. Underhill, Alan Aderem, Kouetsu Ogasawara

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The innate immune system has developed to acquire a wide variety of pattern-recognition receptors (PRRs) to identify potential pathogens, whereas pathogens have also developed to escape host innate immune responses. ITIM-bearing receptors are attractive targets for pathogens to attenuate immune responses against them; however, the in vivo role of the inhibitory PRRs in host-bacteria interactions remains unknown. We demonstrate in this article that Staphylococcus aureus, a major Gram-positive bacteria, exploits inhibitory PRR paired Ig-like receptor (PIR)-B on macrophages to suppress ERK1/2 and inflammasome activation, and subsequent IL-6 and IL-1β secretion. Consequently, Pirb-/- mice infected with S. aureus showed enhanced inflammation and more effective bacterial clearance, resulting in resistance to the sepsis. Screening of S. aureus mutants identified lipoteichoic acid (LTA) as an essential bacterial cell wall component required for binding to PIR-B and modulating inflammatory responses. In vivo, however, an LTA-deficient S. aureus mutant was highly virulent and poorly recognized by macrophages in both wild-type and Pirb-/- mice, demonstrating that LTA recognition by PRRs other than PIR-B mediates effective bacterial elimination. These results provide direct evidence that bacteria exploit the inhibitory receptor for virulence, and host immune system counterbalances the infection.

Original languageEnglish
Pages (from-to)5903-5911
Number of pages9
JournalJournal of Immunology
Volume189
Issue number12
DOIs
Publication statusPublished - 2012 Dec 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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