Author:
Shimizu Takashi,Kimura Yui,Kida Yutaka,Kuwano Koichi,Tachibana Masato,Hashino Masanori,Watarai Masahisa
Abstract
ABSTRACTMycoplasma pneumoniaecauses pneumonia, tracheobronchitis, pharyngitis, and asthma in humans. The pathogenesis ofM. pneumoniaeinfection is attributed to excessive immune responses. We previously demonstrated thatM. pneumoniaelipoproteins induced inflammatory responses through Toll-like receptor 2 (TLR2). In the present study, we demonstrated thatM. pneumoniaeinduced 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 overgrownM. pneumoniaefailed 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 inatpCencoding an ATP synthase F0F1 ε subunit andF10_orf750encoding hypothetical protein MPN333. These mutants showed deficiencies in cytadherence. These results suggest that cytadherence ofM. pneumoniaeinduces inflammatory responses through TLR4 and autophagy.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
60 articles.
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