Pneumococcal pneumonia: mechanisms of infection and resolution.
Chest. 2012 Aug 1;142(2):482-91
Authors: Dockrell DH, Whyte MK, Mitchell TJ
Abstract
Vaccination and antimicrobial therapy remain the cornerstones of the management of pneumococcal pneumonia. Despite significant successes, the capacity of the pneumococcus to evolve in the face of the selective pressure of anticapsular immunity challenges immunization programs. Treatment focuses on antimicrobial therapy but ignores the central role of the dysregulated inflammatory response during pneumonia. Future therapeutic approaches need to build on the considerable recent advances in our understanding of the pathogenesis of pneumococcal pneumonia, including those from models of pneumonia. Enhancement of the essential components of the host response that prevents most colonized individuals from developing pneumonia and strategies to limit inappropriate inflammatory responses to lower respiratory tract infection are approaches that could be exploited to improve disease outcome. This review highlights recent discoveries relating to the microbial and host determinants of microbial clearance and regulation of the inflammatory response, which provide clues as to how this could be achieved in the future.From the Department of Infection and Immunity (Drs Dockrell and Whyte), University of Sheffield Medical School and Sheffield Teaching Hospitals, Sheffield; and the School of Immunity and Infection (Dr Mitchell), College of Medical and Dental Sciences, University of Birmingham, Birmingham, England.Correspondence to: David H. Dockrell, MD, Department of Infection and Immunity, The University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, England; e-mail: d.h.dockrell@sheffield.ac.ukFinancial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Whyte has received travel support for scientific meetings from Boehringer Ingelheim GmbH. She has received competitive external grant funding from a number of noncommercial sources, including the Medical Research Council (MRC) and the Wellcome Trust. Dr Dockrell has received grant support from the Wellcome trust and the MRC. He has received financial support to attend clinical meetings from ViiV Healthcare, Gilead, Bristol-Myers Squibb, Merck Sharp & Dohme Corp and Janssen-Cilag Pty Limited, and has received grant support from Novartis AG. Dr Mitchell has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscriptFunding/Support: This work is supported by a Wellcome Trust Senior Clinical Fellowship to Dr Dockrell (076945) and by Wellcome Trust and Medical Research Council (MRC) grants to Drs Dockrell, Whyte, and Mitchell. Drs Dockrell and Whyte are also funded as part of the MRC-Association of the British Pharmaceutical Industry COPD consortium and the TJM laboratory by the European Community's Seventh Framework Programme under Grant Agreement No. HEALTH-F3-2009-223111 (CAREPNEUMO).This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Information for commercial entities is available online.
PMID: 22871758 [PubMed - in process]