Infect Immun. 2014 Aug 25. pii: IAI.02251-14. [Epub ahead of print]
MicroRNA-155 is required for the clearance of Streptococcus pneumoniae from the nasopharynx.
Verschoor CP1, Dorrington MG1, Novakowski KE1, Kaiser J2, Radford K3, Nair P3, Anipindi V1, Kaushic C1, Surette MG2, Bowdish DM4.
Author information
Abstract
Pneumonia caused by Streptococcus pneumoniae is a major cause of death and economic burden worldwide. S. pneumoniae is an intermittent colonizer of the human upper respiratory tract and the ability to control asymptomatic colonization determines the likelihood of developing invasive disease. Recognition of S. pneumoniae by resident macrophages via TLR-2 and MARCO and the presence of IL-17 secreting CD4+ T-cells are required for macrophage recruitment and bacterial clearance. Despite the fact that the primary cellular effectors needed for bacterial clearance have been identified, much of the underlying regulatory mechanisms are unknown. Herein we demonstrate that the small, non-coding RNA, microRNA-155 (mir-155) is critical for the effective clearance of S. pneumoniae. Our studies show that mir-155 deficient mice maintain the ability to prevent acute, invasive pneumococcal infection, but have significantly higher bacterial burdens following colonization, independent of macrophage recognition by TLR-2, MARCO expression, or bactericidal capacity. The observed defects in bacterial clearance parallel reduced IL-17A and IFN-gamma CD4+ T-cell responses in vivo, lower IL-17A mRNA in the nasopharynx and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in their capacity to generate high titre S. pneumoniae specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary S. pneumoniae colonization.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25156727 [PubMed - as supplied by publisher]
No comments:
Post a Comment