Abstract
BackgroundAging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.MethodsThis cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.ResultsHIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16+ monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8+ T lymphocytes.ConclusionsQuantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10–14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.
Highlights
HIV positive individuals are at a greater risk than their seronegative counterparts of a range of conditions usually associated with aging such as cardiovascular disease [1], osteoporosis [2], frailty [3] and neurocognitive decline [4]
We have recently shown that, when adjusted for age, healthy females have elevated plasma levels of CXCL10 and soluble CD163 (sCD163) and decreased soluble CD14 (sCD14) compared with males [14]
Plasma levels of sCD163 (p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and CXCL10 (p,0.001) were significantly elevated in HIV positive compared with HIV negative women (Table 2)
Summary
HIV positive individuals are at a greater risk than their seronegative counterparts of a range of conditions usually associated with aging such as cardiovascular disease [1], osteoporosis [2], frailty [3] and neurocognitive decline [4]. These conditions are associated in the elderly with elevated levels of inflammatory markers including IL-6 and TNF [5,6]. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women
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