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Inhibitory receptor paired Ig-like receptor B is exploited by Staphylococcus aureus for virulence.
Nakayama, Masafumi,Kurokawa, Kenji,Nakamura, Kyohei,Lee, Bok Luel,Sekimizu, Kazuhisa,Kubagawa, Hiromi,Hiramatsu, Keiichi,Yagita, Hideo,Okumura, Ko,Takai, Toshiyuki,Underhill, David M,Aderem, Alan,Ogas American Association of Immunologists 2012 Journal of Immunology Vol. No.
<P>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.</P>
Inhibitory Effect of Honeybee-Collected Pollen on Mast Cell Degranulation In Vivo and In Vitro
Yasuko Ishikawa,Tomoko Tokura,Nobuhiro Nakano,Mutsuko Hara,Fran?is Niyonsaba,Hiroko Ushio,Yuji Yamamoto,Tadahiro Tadokoro,Ko Okumura,Hideoki Ogawa 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.1
Bee-collected pollen (bee pollen [BP]) has been used as a folk medicine for centuries against various diseases,including allergy. There is no study elucidating how BP exerts such an anti-allergic effect. Since mast cells play a central rolein the pathogenesis of various allergic diseases, we investigated the effect of BP on mast cell activation elicited by the Fc im-munoglobulin E (IgE) receptor (Fc.RI)-mediated pathways. The in vivo effect of orally administered BP on cutaneous mastcell activation was examined by passive cutaneous anaphylaxis reaction. In vitromast cell degranulation and IgE binding tomast cells and the status of protein tyrosine phosphorylation were examined using bone marrow-derived mast cells. Daily oraladministration of BP to mice significantly reduced the cutaneous mast cell activation elicited by IgE and specific antigens.BP also reduced in vitromast cell degranulation and tumor necrosis factor-. production by inhibiting IgE binding to Fc.RIon mast cells. The inhibitory effect of BP on mast cell degranulation by preventing IgE binding was confirmed by the re-duced levels of protein tyrosine phosphorylation, which occurred as downstream events in activated mast cells via Fc.RI.These results first revealed that the anti-allergic action of BP was exerted by inhibiting the Fc.RI-mediated activation of mastcells, which plays important roles, not only in the early phase, but also in the late phase of allergic reactions.