title: Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus aureus for virulence.
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.
authors.affiliation: Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan. mnakayama@idac.tohoku.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Kyohei
authors.initials: K
authors.lastname: Nakamura
authors.forename: Bok Luel
authors.initials: BL
authors.lastname: Lee
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kubagawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology*
chemical_list: D058847:Inflammasomes; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic