Monocyte-Independent and -Dependent Regulation of Regulatory T-Cell Development in <i>Mycoplasma</i> Infection
Ryo Takahashi, Tetsuo Shiohara, Yoshiko Mizukawa
Abstract
BACKGROUND: Although Mycoplasma pneumoniae (MP) infection has been implicated in the pathogenesis of allergic diseases, the mechanism of this trigger remains unknown. We explored the mechanism for how MP infection could tilt the balance between regulatory T cells (Tregs) and Th17 cells. METHODS: We analyzed the frequency, phenotype, and function of Tregs in patients at the different stages of MP and various virus infections over a period of more than 1 year. We examined the effect of monocytes to elucidate signals that can regulate the balance between Treg and Th17 cells. RESULTS: The functional activity of Tregs was profoundly impaired during the acute stage of MP as well as viral infections. Upon resolution, however, the Treg function remained impaired even 1 year after MP infection. In the resolution stage, the impaired Treg function was associated with an increase in interleukin (IL) 17A+ Tregs and Th17 cells. Development of Th17 cells was dependent on the "aberrant" proinflammatory monocytes (pMOs), characterized by potent ability to produce IL-6 in a Toll-like receptor 2-dependent manner. CONCLUSIONS: Depending on the prevalence of the pMOs, Tregs and Th17 cells could mutually regulate the number and function of the other. The pMOs/IL-6 could be crucial therapeutic targets against MP-induced allergic diseases.