Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.
Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline.
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
Rebeca Sara
RS
de Pablo-Bernal
Heliopolis nursing home, Seville, Spain.
Julio
J
Cañizares
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
Isaac
I
Rosado
Heliopolis nursing home, Seville, Spain.
María Isabel
MI
Galvá
Department of Clinical Biochemistry, Virgen del Rocío University Hospital IBiS/CSIC/SAS/University of Seville, Spain.
Ana Isabel
AI
Alvarez-Ríos
Department of Medical Biochemistry and Molecular Biology and Immunology, University of Seville School of Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain. Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)-Instituto de Salud Carlos III, Seville, Spain.
Antonio
A
Carrillo-Vico
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland.
Sara
S
Ferrando-Martínez
Laboratory of Molecular Immuno-Biology Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
María Ángeles
MÁ
Muñoz-Fernández
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain. Department of Biochemistry and Molecular Biology and Immunology, Medical School, University of Seville, Spain.
Mohammed
M
Rafii-El-Idrissi Benhnia
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
Yolanda María
YM
Pacheco
Heliopolis nursing home, Seville, Spain.
Raquel
R
Ramos
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
Manuel
M
Leal
Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
Ezequiel
E
Ruiz-Mateos
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood* / Q000821:virology; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000523:psychology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000502:physiology*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015703:Antigens, CD; D007074:Immunoglobulin G; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha
Aging; CMV; Cognitive; Inflammation; Mini-mental; Monocyte function