title: Cytadherence of Mycoplasma pneumoniae induces inflammatory responses through autophagy and toll-like receptor 4.
abstract: Mycoplasma pneumoniae causes pneumonia, tracheobronchitis, pharyngitis, and asthma in humans. The pathogenesis of M. pneumoniae infection is attributed to excessive immune responses. We previously demonstrated that M. pneumoniae lipoproteins induced inflammatory responses through Toll-like receptor 2 (TLR2). In the present study, we demonstrated that M. pneumoniae induced strong inflammatory responses in macrophages derived from TLR2 knockout (KO) mice. Cytokine production in TLR2 KO macrophages was increased compared with that in the macrophages of wild-type (WT) mice. Heat-killed, antibiotic-treated, and overgrown M. pneumoniae failed to induce inflammatory responses in TLR2 KO macrophages. 3-Methyladenine and chloroquine, inhibitors of autophagy, decreased the induction of inflammatory responses in TLR2 KO macrophages. These inflammatory responses were also inhibited in macrophages treated with the TLR4 inhibitor VIPER and those obtained from TLR2 and TLR4 (TLR2/4) double-KO mice. Two mutants that lacked the ability to induce inflammatory responses in TLR2 KO macrophages were obtained by transposon mutagenesis. The transposons were inserted in atpC encoding an ATP synthase F0F1 ε subunit and F10_orf750 encoding hypothetical protein MPN333. These mutants showed deficiencies in cytadherence. These results suggest that cytadherence of M. pneumoniae induces inflammatory responses through TLR4 and autophagy.
authors.affiliation: Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Yamaguchi, Japan shimizut@yamaguchi-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kida
authors.affiliation: Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kuwano
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hashino
authors.affiliation: Laboratory of Veterinary Public Health, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Yamaguchi, Japan The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Watarai
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001422:Bacterial Adhesion / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009175:Mycoplasma Infections / Q000276:immunology* / Q000382:microbiology; D009177:Mycoplasma pneumoniae / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4