Objective:

Antibody responses are often impaired in old age and in HIV-positive (HIV+) infection despite virologic control with antiretroviral therapy but innate immunologic determinants are not well understood.

Design:

Monocytes and natural killer cells were examined for relationships to age, HIV infection and influenza vaccine responses.

Methods:

Virologically suppressed HIV+(n= 139) and HIV-negative (HIV−)(n= 137) participants classified by age as young (18–39 years), middle-aged (40–59 years) and old (≥ 60 years) were evaluated preinfluenza and postinfluenza vaccination.

Results:

Prevaccination frequencies of inflammatory monocytes were highest in old HIV+ and HIV−, with old HIV+ exhibiting higher frequency of integrin CD11b on inflammatory monocytes that was correlated with age, expression of CC chemokine receptor-2 (CCR2) and plasma soluble tumor necrosis factor receptor-1 (sTNFR1), with inverse correlation with postvaccination influenza H1N1 antibody titers. Higher frequencies of CD11b+ inflammatory monocytes (CD11b hi,> 48.4%) compared with low frequencies of CD11b+ inflammatory monocytes (< 15.8%) was associated with higher prevaccination frequencies of total and inflammatory monocytes and higher CCR2 MFI, higher plasma sTNFR1 and CXCL-10 with higher lipopolysaccharide stimulated expression of TNFα and IL-6, concomitant with lower postvaccination influenza antibody titers. In HIV+ CD11b hi expressers, the depletion of inflammatory monocytes from peripheral blood mononuclear cells resulted in enhanced antigen-specific CD4+ T-cell proliferation. Immature CD56 hi natural killer cells were lower in young HIV+ compared with young HIV− participants.

Conclusion:

Perturbations of innate immunity and inflammation signified by high CD11b on inflammatory monocytes are exacerbated with aging in HIV+ and negatively impact immune function involved in Ab response to influenza vaccination.