title: Macrophages activated by Listeria monocytogenes induce organ-specific autoimmunity.
abstract: We have previously reported an experimental autoimmune model induced by the local infection of Listeria monocytogenes. The unilateral inoculation of virulent Listeria into a testis of a normal mouse induced a delayed-type hypersensitivity response against testicular antigen and caused autoimmune orchitis in the contralateral testis. The orchitis was transferred to naive mice by T cells from the intratesticularly infected mice. In this paper, we demonstrated that avirulent Listeria, which lacks the expression of listeriolysin O, failed to induce any anti-testicular responses or contralateral orchitis even when it was inoculated at a high dose into the testis. Furthermore, the intraperitoneal inoculation of virulent Listeria with testicular antigen induced the anti-testicular responses and orchitis although intraperitoneal inoculation of testicular antigen with avirulent Listeria failed to induce them. The difference between virulent and avirulent Listeria in the induction of anti-testicular responses was supposed to be dependent on the difference in macrophage activation by the two bacterial strains because, first, the anti-testicular responses were elicited in normal mice when macrophages from virulent Listeria-infected mice were intraperitoneally transferred with testicular antigen although no viable bacteria were detected from the macrophages, and secondly, in contrast, the intraperitoneal co-inoculation of macrophages from avirulent Listeria-infected mice and testicular antigen failed to elicit any anti-testicular responses. Finally, we found that the virulent Listeria-induced macrophages expressed a higher level of CD80 (B7-1) and CD86 (B7-2) molecules than did the avirulent Listeria-induced macrophages and naive peritoneal macrophages. These results thus suggest that virulent Listeria activates macrophages to induce autoreactive T cells while avirulent Listeria does not. The up-regulation of B7 molecules by virulent Listeria infection is a candidate of the mechanism for the activation of autoreactive T cells.
authors.affiliation: Department of Immunology, Kyushu University, Fukuoka, Japan.
authors.forename: K H
authors.initials: KH
authors.lastname: Sonoda
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: A
authors.initials: A
authors.lastname: Nomura
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Hamano
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Mukasa
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D008089:Listeria monocytogenes / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009920:Orchitis / Q000276:immunology* / Q000473:pathology; D013737:Testis / Q000276:immunology; D015854:Up-Regulation; D014774:Virulence
chemical_list: D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins