Abstract
Mycoplasmas cause respiratory diseases characterized by persistent infection and chronic airway inflammation. Mycoplasma lung disease is immunopathologic, with CD4+ Th cells determining both disease severity and resistance to infection. Th2 cell responses promote immunopathology, while Th1 cells confer resistance to infection. However, regulatory CD4+ T cells may also have a role in the pathogenesis of mycoplasma respiratory diseases. We hypothesized Treg cells control the severity of the inflammatory lesions and may also promote persistence of infection. To examine this, BALB/c mice were depleted of CD25+ cells, and had increased disease severity due to Mycoplasma pulmonis infection. Increases in mycoplasma antibody responses and lymphocyte infiltration into lungs also occurred after CD25+ cell depletion. CD4+CD25+ regulatory T cells promoted IFN-γ and IL-17 mycoplasma-specific CD4+ T cell responses in vitro and in vivo, while dampening IL-13+ Th responses. Neither IL-10 nor TGF-ß expression was detected in CD4+CD25+ T cells from lymph nodes. Thus, a regulatory T cell population plays an important role in controlling damaging immune responses in mycoplasma respiratory disease but does not contribute to persistence of infection. It appears that a regulatory T cell population preferentially dampens Th2 cell-mediated inflammatory responses to mycoplasma through a mechanism independent of IL-10 or TGF-ß characteristic of “classic” Treg cells.
Highlights
Mycoplasmas cause respiratory diseases in humans and animals
Total numbers of T regulatory (Treg) cells increase in the draining lymph nodes during the course of M. pulmonis infection, and display a classical Treg phenotype
In order to determine the changes in Treg numbers along the lower respiratory tract during mycoplasma disease pathogenesis, mice were intranasally infected with M. pulmonis and sacrificed at various time points
Summary
Mycoplasmas cause respiratory diseases in humans and animals. Mycoplasma pneumoniae causes up to 30% of all community-acquired pneumonia cases each year, and is commonly referred to as “walking pneumonia” [1]. Mycoplasma respiratory diseases are typically characterized by high morbidity and low mortality, with infections persisting for weeks, some requiring hospitalization (more than 100,000 people each year). Mycoplasma infections are linked with exacerbation of a number of other diseases, including increased severity of PLOS ONE | DOI:10.1371/journal.pone.0155648. Previous work using the murine pathogen Mycoplasma pulmonis has revealed that a large component of the immune response is immunopathologic [5, 6], and T cell responses and their regulation are critical in determining the severity of disease [7,8,9]. Other cell populations can modulate mycoplasma disease [7, 11, 12], the role of Treg cells in mycoplasma respiratory diseases has not yet been examined
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