Cytadherence of mycoplasma pneumoniae induces inflammatory responses through autophagy and toll-like receptor 4

Takashi Shimizu, Yui Kimura, Yutaka Kida, Koichi Kuwano, Masato Tachibana, Masanori Hashino, Masahisa Watarai

Research output: Contribution to journalArticle

25 Citations (Scopus)

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, antibiotictreated, 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 e{open} 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.

Original languageEnglish
Pages (from-to)3076-3086
Number of pages11
JournalInfection and Immunity
Volume82
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Toll-Like Receptor 2
Mycoplasma pneumoniae
Toll-Like Receptor 4
Autophagy
Macrophages
Knockout Mice
Pharyngitis
Chloroquine
Mutagenesis
Lipoproteins
Pneumonia
Asthma
Hot Temperature
Adenosine Triphosphate
Cytokines
Infection

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Cytadherence of mycoplasma pneumoniae induces inflammatory responses through autophagy and toll-like receptor 4. / Shimizu, Takashi; Kimura, Yui; Kida, Yutaka; Kuwano, Koichi; Tachibana, Masato; Hashino, Masanori; Watarai, Masahisa.

In: Infection and Immunity, Vol. 82, No. 7, 2014, p. 3076-3086.

Research output: Contribution to journalArticle

Shimizu, Takashi ; Kimura, Yui ; Kida, Yutaka ; Kuwano, Koichi ; Tachibana, Masato ; Hashino, Masanori ; Watarai, Masahisa. / Cytadherence of mycoplasma pneumoniae induces inflammatory responses through autophagy and toll-like receptor 4. In: Infection and Immunity. 2014 ; Vol. 82, No. 7. pp. 3076-3086.
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