Aging of the human innate immune system in HIV infection

Abstract

HIV infection is associated with a chronic inflammatory state arising from multiple factors, including innate immune recognition of HIV, increased microbial translocation, and release of endogenous ligands from damaged cells (such as CD4 T cells). In many respects, this heightened pro-inflammatory environment resembles that associated with aging in the absence of HIV infection, and evidence of dysregulated innate immune responses can be found in not only older HIV-negative adults, but also adults with HIV infection. While the study of innate immune aging in HIV infection is still in its early stages, it seems likely that at least additive, or potentially synergistic effects of aging and HIV infection will be found.

Figure 1

Comparison of effects of HIV and aging on innate immune responses. Both HIV and Aging are accompanied by pro-inflammatory environments that are likely to be triggered by elevated levels of pattern recognition ligands (Pathogen-Associated Molecular patterns (PAMPS) and Damage-Associated Molecular Patterns (DAMPS)). Toll-like receptors (TLR) and IFN-α receptor (IFNAR) are depicted. Increases or decreases in TLR-induced cytokine responses are shown by arrows (blue arrow: DC, Orange arrow: Monocytes, Green arrow; Monocyte-derived DC). Abbreviations: IFN, Interferon; mtDNA, mitochondrial DNA; TERT, Telomerase reverse transcriptase; NRTIs, nucleotide reverse transcriptase inhibitors; LPS, Lipopolysaccharide. TLR8 induced TNF-α is decreased in mDC at the earliest stages of infection