ICMI 2015

T.5 A member of plant rhizosphere microbiota, Stenotrophomonas maltophilia, creates MyD88/IL-10 mediated intracellular co-habitation niche in murine colonic macrophage.

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Ichiro Takahashi, DDS, PhD , Hiroshima University, Graduate School of Biomedical Sciences, Dept. of Mucosal Immunology, Hiroshima, Hiroshima, Japan
Daiki Yamamoto, DDS , Hiroshima University Hospital, Hiroshima, Japan
Yosuke Kurashima, PhD , Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Naoko Shibata, PhD , Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Yoshiyuki Goto, PhD , Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Jun Kunisawa, PhD , Laboratory of Vaccine Material, NIBIOHN, Ibaraki-Osaka, Japan
Shintaro Sato, PhD , Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Hiroshi Kiyono, DDS, PhD , Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
We surprisingly noticed, by using 16S-rRNA-based metagenome analysis, the existence of Stenotrophomonas maltophilia, a member of plant rhizosphere microbiota, in the colonic resident macrophage in BALB/c mice. In order to clarify the molecular basis behind the symbiotic existence of the rhizosphere bacteria in macrophage, we initially performed confocal laser and transmission electron microscopic analyses of S. maltophilia in murine bone marrow (BM) derived macrophage. It was revealed that S. maltophilia was constitutively resident in not only endosome but also cytosol of BALB/c BM macrophage. The same analyses by using innate immunity-related gene deficient BM macrophage suggested that MyD88/IL-10 was absolutely required for cytosol and endosomal existence, while NLRP3/procaspase-1 exclusively required for cytosol habitation. This cytosol habitation should be triggered by a S. maltophilia secreting molecule designated as “smlt2713”, because the smlt2713 gene-deficient S. maltophilia strain was not able to establish cytosol cohabitation, and instead made aberrantly giant S. maltophilia containing vacuoles in macrophage. We speculate the smlt2713 protein might constitutively activate NLRP3/procaspase-1 complex and create a symbiotic environment in tissue resident macrophage.  Since the smlt2713 protein and/or the smlt2713 protein possessing S. maltophilia showed the ability to produce IL-10 by BM-macrophage in NLRP3/procaspase-1 as well as MyD88 dependent manner, the rhizosphere-derived bacteria might create and maintain an immunologically symbiotic condition in the colon via a unusual cytosolic PRR (NLRP3/procaspase-1) and endosomal PRR (MyD88/TIRAP) signaling interaction.