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The mechanisms involved in the TLR-mediated cytokine response are well established; however, the possible contribution of TLR-dependent recognition of bacteria to macrophage phagocytosis remains unclear.<jats:italic>Listeria monocytogenes<\/jats:italic>is an intracellular, parasitic, Gram-positive bacterium recognized mainly by TLR2. In this study, we investigated whether TLR2-dependent signaling is involved in the phagocytosis of<jats:italic>L. monocytogenes<\/jats:italic>by macrophages. We found no difference in the number of<jats:italic>L. monocytogenes<\/jats:italic>cells associating with wild-type (WT) and TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>macrophages 1 h after infection. However, the number of<jats:italic>L. monocytogenes<\/jats:italic>cells phagocytosed in TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>and MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>macrophages was significantly lower than that of WT macrophages. In addition, lipopolysaccharide (LPS) treatment restored impaired phagocytic activity of TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>macrophages but did not enhance the activity of MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>macrophages. The efficiency of phagocytosis was suppressed by inhibitors of phosphatidylinositol 3-kinase (PI3K) and the small Rho GTPases but not by cycloheximide. Moreover, functional activation of PI3K and Rac1 was impaired in TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>and MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>macrophages. In an<jats:italic>in vivo<\/jats:italic>infection model, we found significantly lower numbers of<jats:italic>L. monocytogenes<\/jats:italic>cells phagocytosed in peritoneal macrophages of TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>and MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice after intraperitoneal infection. Moreover, a lower number of bacteria were detected in the spleens of TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice 1 day after intravenous infection than in WT mice. These results clearly indicated that TLR2-MyD88-dependent signaling enhances the basal level of phagocytosis of<jats:italic>L. monocytogenes<\/jats:italic>by macrophages through activation of PI3K and Rac1, not by synthesis of proinflammatory cytokines or expression of phagocytic receptors.<\/jats:p>","DOI":"10.1128\/iai.01138-09","type":"journal-article","created":{"date-parts":[[2010,4,6]],"date-time":"2010-04-06T00:26:28Z","timestamp":1270513588000},"page":"2857-2867","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":70,"title":["Toll-Like Receptor 2- and MyD88-Dependent Phosphatidylinositol 3-Kinase and Rac1 Activation Facilitates the Phagocytosis of<i>Listeria monocytogenes<\/i>by Murine Macrophages"],"prefix":"10.1128","volume":"78","author":[{"given":"Yanna","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita R.","family":"Dewamitta","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixin","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Daim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Mitsuyama","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(98)80062-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.6.731"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838718"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2003.10.005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096158"},{"key":"e_1_3_2_8_2","first-page":"6615","volume":"19","year":"2007","unstructured":"Bosse, T., J. 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