TY - JOUR
T1 - Regulatory CD4+ CD25+ T cells dampen inflammatory disease in murine mycoplasma pneumonia and promote IL-17 and IFN-γ Responses
AU - Odeh, Adam N.
AU - Simecka, Jerry W.
N1 - Funding Information:
Both authors were involved in the experimental design, interpretation and writing of the manuscript. Dr. Adam Odeh’s performed these studies under the guidance of Dr. Simecka. The authors would like to thank Dr. Xiangle Sun for her excellent assistance. We would like to thank Drs. Rance Berg, Lisa Hodge and Nicole Dobbs for their useful discussions and support. Flow cytometry was performed in the Flow Cytometry and Laser Capture Microdissection Core Facility at The University of North Texas Health Science Center. This work was supported by Public Health Service Grant R01AI042075 (to J.W.S.). Flow Cytometry facility was supported a shared instrument grant from the National Institutes of Health.
Publisher Copyright:
© 2016 Odeh, Simecka. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/5
Y1 - 2016/5
N2 - 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-ã 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-β 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-β characteristic of "classic" Treg cells.
AB - 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-ã 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-β 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-β characteristic of "classic" Treg cells.
UR - http://www.scopus.com/inward/record.url?scp=84971221964&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0155648
DO - 10.1371/journal.pone.0155648
M3 - Article
C2 - 27175511
AN - SCOPUS:84971221964
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e0155648
ER -