title: Prevention of allograft tolerance by bacterial infection with Listeria monocytogenes.
abstract: Exposure to certain viruses and parasites has been shown to prevent the induction of transplantation tolerance in mice via the generation of cross-reactive memory T cell responses or the induction of bystander activation. Bacterial infections are common in the perioperative period of solid organ allograft recipients in the clinic, and correlations between bacterial infections and acute allograft rejection have been reported. However, whether bacterial infections at the time of transplantation have any effect on the generation of transplantation tolerance remains to be established. We used the Gram-positive intracellular bacterium Listeria monocytogenes (LM) as a model pathogen because its effects on immune responses are well described. Perioperative LM infection prevented cardiac and skin allograft acceptance induced by anti-CD154 and donor-specific transfusion in mice. LM-mediated rejection was not due to the generation of cross-reactive T cells and was largely independent of signaling via MyD88, an adaptor for most TLRs, IL-1, and IL-18. Instead, transplant rejection following LM infection was dependent on the expression of the phagosome-lysing pore former listeriolysin O and on type I IFN receptor signaling. Our results indicate that bacterial exposure at the time of transplantation can antagonize tolerogenic regimens by enhancing alloantigen-specific immune responses independently of the generation of cross-reactive memory T cells.
authors.affiliation: Section of Transplantation, Department of Surgery, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Tongmin
authors.initials: T
authors.lastname: Wang
authors.forename: Luqiu
authors.initials: L
authors.lastname: Chen
authors.forename: Emily
authors.initials: E
authors.lastname: Ahmed
authors.forename: Lianli
authors.initials: L
authors.lastname: Ma
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Honglin
authors.initials: H
authors.lastname: Xu
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism; D024201:Bystander Effect / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016027:Heart Transplantation / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology* / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007370:Interferon Type I; D007375:Interleukin-1; D020382:Interleukin-18; D007519:Isoantigens; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; C038705:hlyA protein, Listeria monocytogenes