Anti-pneumococcal deficits of monocyte-derived macrophages from the advanced-age, frail elderly and related impairments in PI3K-AKT signaling

Abstract The advanced-age, frail elderly are especially vulnerable to developing pneumococcal infection and disease. Macrophages are critical mediators in the defence against Streptococcus pneumoniae at the upper respiratory tract, however, little is known of their anti-pneumococcal capacity in the...

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Bibliographic Details
Published in:Human immunology 2014-12, Vol.75 (12), p.1192-1196
Main Authors: Verschoor, Chris P, Johnstone, Jennie, Loeb, Mark, Bramson, Jonathan L, Bowdish, Dawn M.E
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Aged, 80 and over
Aging
AKT
Allergy and Immunology
Androstadienes - pharmacology
Chromones - pharmacology
Cytokine
Disease Susceptibility - immunology
Frail Elderly
Humans
Interleukin-1beta - biosynthesis
Interleukin-6 - biosynthesis
Interleukin-8 - biosynthesis
Macrophage
Macrophages - immunology
Middle Aged
Morpholines - pharmacology
Phagocytosis - immunology
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - immunology
Pneumonia, Pneumococcal - immunology
Pneumonia, Pneumococcal - microbiology
Pneumonia, Pneumococcal - mortality
Proto-Oncogene Proteins c-akt - immunology
Signal Transduction - immunology
Streptococcus pneumoniae
Streptococcus pneumoniae - immunology
Tumor Necrosis Factor-alpha - biosynthesis
Wortmannin
Young Adult
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Summary:Abstract The advanced-age, frail elderly are especially vulnerable to developing pneumococcal infection and disease. Macrophages are critical mediators in the defence against Streptococcus pneumoniae at the upper respiratory tract, however, little is known of their anti-pneumococcal capacity in the elderly. Herein we demonstrate that monocyte-derived macrophages (MDMs) from the advanced-age, frail elderly produce less TNF, IL-6, IL-1β and IL-8 in response to heat-killed S. pneumoniae , which does not appear to be related to mRNA stability or decay. Furthermore, despite maintaining the ability to bind and phagocytose bacteria, MDMs from these individuals have a reduced capacity to kill S. pneumoniae . These defects parallel reduced PI3K-AKT signaling, which can significantly abrogate bacterial killing, but does not affect cytokine responses. Since macrophages are critical in the defence against S. pneumoniae , this study adds valuable insight into the susceptibility of the elderly to pneumococcal disease and highlights the PI3K-AKT signaling pathway as a potential therapeutic target.
ISSN:0198-8859
1879-1166
DOI:10.1016/j.humimm.2014.10.004