Elevated plasma lipopolysaccharide is not sufficient to drive natural killer cell activation in HIV-1-infected individuals.
BACKGROUND
Lipopolysaccharide (LPS) is elevated in the plasma of individuals chronically infected with HIV-1 and is thought to contribute to chronic immune activation of myeloid cells and T-cells. Natural killer (NK) cells can also be stimulated by LPS in vitro.


OBJECTIVE
To measure plasma LPS levels in individuals with HIV-1 infection, with or without suppressed plasma viral load, and in individuals with or without inflammatory bowel diseases (IBD). To compare the expression of NK cell receptors and activation markers in individuals with HIV-1 infection and in HIV-1-negative individuals with active IBD.


METHODS
NK cells were studied by flow cytometry in treatment-naïve viraemic HIV-1-positive individuals (n = 14), aviraemic HIV-1-positive individuals (n = 19), HIV-1-negative individuals with inflammatory bowel disease (n = 10) and HIV-1-negative healthy control individuals (n = 17). Plasma endotoxin (LPS) was measured using the limulus amoebocyte assay.


RESULTS
Viraemic and aviraemic HIV-1-positive individuals and patients with IBD have elevated levels of plasma LPS compared with HIV-1-negative individuals.HIV-1-positive individuals had significant changes in activation marker or NK cell receptor expression, whereas NK cells from IBD patients had similar levels to HIV-1-negative controls. NK cells from HIV-1-positive individuals are refractory to further stimulation by LPS in vitro.


CONCLUSIONS
Elevated plasma LPS alone does not account for the chronic activation and receptor loss in NK cells from HIV-1-infected individuals.
Gregson
John Ns
JN
Department of Immunology, Imperial College London, UK.
Steel
Alan
A
Bower
Mark
M
Gazzard
Brian G
BG
Gotch
Frances M
FM
Goodier
Martin R
MR
D000328:Adult; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000097:blood*; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D055607:Receptors, Natural Killer Cell / Q000097:blood; D019562:Viral Load; D055815:Young Adult
D008070:Lipopolysaccharides; D055607:Receptors, Natural Killer Cell