T Regulatory Cells Control Susceptibility to Invasive Pneumococcal Pneumonia in Mice

• DOI: 10.1371/journal.ppat.1002660
• Publication Date: 2012-04-19T20:52:21Z
• Authors: Daniel R. Neill; Vitor E. Fernandes; Laura Wisby; Andrew R. Haynes; Daniela M. Ferreira; Ameera Laher; Natalie Strickland; Stephen B. Gordon; Paul Denny; Aras Kadioglu; Peter W. Andrew
• Keywords: Pneumococcal pneumonia; Pneumococcal infections; Adoptive Cell Transfer; Regulatory T cell

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 known about role played by immunoregulatory cells cytokines control such responses. We demonstrate considerable differences immunomodulatory cytokine transforming growth factor (TGF)-β between pneumonia resistant BALB/c susceptible CBA/Ca mouse strains. Immunohistochemistry flow cytometry reveal higher levels TGF-β protein lungs that correlates with rapid rise Foxp3+Helios+ T regulatory cells. These have protective functions pneumonia, because blocking their induction inhibitor impairs resistance to aids bacterial dissemination from lungs. Conversely, adoptive transfer mice, prior infection, prolongs survival decreases blood. Importantly, strong cell responses also correlate disease-resistance outbred MF1 confirming importance controlling pneumococcus. This study provides exciting new evidence immunomodulation pulmonary suggests signalling potential target immunotherapy or drug design.