Monocytes in chronic HIV-1 infection : changes in phenotypic marker expression and their relationship with immune activation

[摘要] ENGLISH ABSTRACT: HIV-infection is characterized by depletion of CD4+ T-cells from the gut-associated lymphoid tissue (GALT) which causes irreparable gastrointestinal tract damage and subsequent microbial translocation of bacterial products such as lipopolysaccharide (LPS), a component of Gram-negative bacteria, into systemic circulation. HIV infection also affects the functions and relative population sizes of various immune cells, such as monocytes. Monocytes are important innate immune cells as they are often the first cells recruited to sites of infection and inflammation. They then either promote inflammatory processes; elicit adaptive immune responses, through their antigen presenting ability; aid in pathogen and debris clearance or aid in damage repair. This cross-sectional study investigated functional changes to monocytes and monocyte subsets (CD14+CD16- and CD14+CD16+) in HIV+, treatment naïve individuals and healthy uninfected controls, using whole blood assays and isolated monocytes. A number of chemokine receptors associated with function and homing, and specific gut-homing receptors, were investigated. Monocyte activation, apoptotic potential and intracellular monocyte cytokine production were also investigated. All markers were evaluated using multi-parameter flow cytometry. Monocyte responsiveness to in vitro LPS stimulation and expression of the afore-mentioned chemokine receptors to viral load, CD4+ count and CD38/8 T-cell expression was also assessed. During HIV-infection monocytes appeared primed to exit systemic circulation and migrate towards the gut, as seen through elevated CD62-L (p < 0.005) and CCR7 (p < 0.005), whereas the CD14+CD16+ subset was increased (p = 0.0461) and exhibited a higher activation status through increased CD69 expression (p < 0.005) compared to the CD14+CD16- subset. An interesting observation was the significantly increased IL-10 production by the CD14+CD16+ subset (p < 0.005). An elevated CCR5 expression in total monocytes (p < 0.005) was also seen. After LPS stimulation, the HIV+ group displayed unique and significant percentage increases in the total monocyte population.The findings of the current study suggest that monocyte functionality may be retained during HIV-infection and that CD14+CD16+ monocytes play a vital role during HIV-infection evidenced by their preferential expansion and priming for GALT migration. The production of IL-10 by this subset further highlights their importance and emphasizes the need for future studies on the role of these cells in chronic stable HIV-1 infection and whilst disease progresses.

[发布机构] Stellenbosch University