Abstract
Streptococcus pneumoniae is the most common cause of severe pneumonia in the elderly. However, the impact of aging on the innate inflammatory response to pneumococci is poorly defined. We compared the innate immune response in old vs. young adult mice following infection with S. pneumoniae. The accumulation of neutrophils recovered from bronchoalveolar lavage fluid and lung homogenates was increased in aged compared with young adult mice, although bacterial outgrowth was similar in both age groups, as were markers of microvascular leak. Aged mice had similar levels of IL-1β, TNF, IFN-γ, IL-17, and granulocyte colony-stimulating factor following S. pneumoniae infection, compared with young mice, but increased levels of the chemokines CXCL9, CXCL12, CCL3, CCL4, CCL5, CCL11, and CCL17. Moreover, levels of IL-10 were significantly lower in aged animals. Neutralization of IL-10 in infected young mice was associated with increased neutrophil recruitment but no decrease in bacterial outgrowth. Furthermore, IL-10 neutralization resulted in increased levels of CCL3, CCL5, and CXCL10. We conclude that aging is associated with enhanced inflammatory responses following S. pneumoniae infection as a result of a compromised immunomodulatory cytokine response.
Highlights
THE BACTERIUM Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP) and the most frequent cause of infectious disease-related admittance to the intensive care unit [32, 33]
Differential cell counts revealed that the number of neutrophils isolated from the bronchoalveolar lavage (BAL) fluid and lung homogenates were significantly higher in aged mice compared with young mice following infection (Fig. 1, C and D), indicating that aged mice mount a heightened innate inflammatory response to S. pneumoniae
In the present study we focused on the acute phase of S. pneumoniae infection and compared the innate immune response in aged vs. young mice
Summary
THE BACTERIUM Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP) and the most frequent cause of infectious disease-related admittance to the intensive care unit [32, 33]. Age-related alterations in the adaptive immune system include an increased production of autoantibodies and decreased production of pneumococcal-specific antibodies [39, 45], decreased T cell proliferative responses [12, 31], and a diminished T cell repertoire [35] These factors are likely to enhance infectious disease susceptibility, exemplified by a higher incidence of infection to a broad spectrum of pathogens, such as influenza virus and S. pneumoniae [6, 8, 19], by the reactivation of tuberculosis [23, 38], and a decrease in vaccine efficacy [39]. These findings have important implications for our understanding of the mechanisms involved in the dysregulation of innate immune responses during aging
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: American Journal of Physiology-Lung Cellular and Molecular Physiology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
