Impaired Functions of Peripheral Blood Monocyte Subpopulations in Aged Humans

Abstract

Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14++(high)CD16−, CD14+(low)CD16−, CD14++(high)CD16+, and CD14+(low)CD16+) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14++(high)CD16+ and CD14+(low)CD16+ monocytes were significantly increased, whereas proportions of CD14+(low)CD16− monocytes were decreased in aged subjects as compared to young subjects. In aged subjects, IL-6 production by all four subsets of monocytes was significantly decreased, whereas TNF-α production was decreased in monocyte subsets, except the CD14+(low)CD16− subset. A significantly reduced expression of TLR1 was observed in CD14++(high)CD16+ and CD14+(low)CD16+ monocyte subsets in aged subjects. Furthermore, following pam3Cys stimulation, ERK1/2 phosphorylation was significantly lower in CD14+(low)CD16+, CD14++(high)CD16+, and CD14+(low)CD16− subsets of monocytes from aged subjects. This is the first study of four subpopulations of monocytes in aging, which demonstrates that their functions are differentially impaired with regard to the production of cytokines, expression of TLR, and signaling via the ERK–MAPK pathway. Finally, changes in the number of monocyte subsets, and impairment of TLR1 expression, TNF-α production, and EK1/2 phosphorylation was more consistent in CD16+ monocyte subsets regardless of expression of CD14high or CD14+low, therefore highlighting the significance of further subdivision of monocytes into four subpopulations.

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…29,[53][54][55][56] This "activated pattern" is confirmed by the expansion of CD11b expression and by the reduction of CD38, CD62L, and CD115 expression. Plasma levels of soluble CD163 (sCD163) and CXCL10, markers of innate immune activation, increase with age.…”

Ageing and the immune system: focus on macrophages

“…In fact, early studies reported increased, unchanged, and decreased LPS-induced cytokine secretion [69]. However, more recently, an age-related reduction in IL-6 production by monocytes in response to TLR1/2 ligand has been demonstrated [76]. In addition, van Duin et al also reported reduced TLR1/2-induced TNF-α and IL-6 production by monocytes from older individuals using fl ow cytometry [77].…”

Assessing immune aging in HIV-infected patients

“…71 Despite relatively few changes in the absolute numbers of monocytes, the distribution of the different subsets is changed, characterized by a marked reduction in classical monocytes and an increased frequency of intermediate and non-classical monocytes in older or HIV infected patients. [72][73][74] These CD16 C monocytes are increased during the infection and are correlated with viremia, T cell activation, and with plasma levels of IL-6. They are expanded in patients who do not take therapy or discontinue treatment.…”