t regulatory cells control susceptibility to invasive pneumococcal pneumonia in micet调节细胞控制容易侵入性肺炎球菌肺炎小鼠.pdf

T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice 1¤ 1 2 2 1,3 Daniel R. Neill , Vitor E. Fernandes , Laura Wisby , Andrew R. Haynes , Daniela M. Ferreira , 1 3 3 2 1¤ Ameera Laher , Natalie Strickland , Stephen B. Gordon , Paul Denny , Aras Kadioglu *, Peter W. Andrew1* 1 Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom, 2 MRC Harwell, Mammalian Genetics Unit, Harwell Science and Innovation Campus, Oxfordshire, United Kingdom, 3 Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom Abstract Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-b between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-b protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+ Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-b impairs BALB/c res