Nef protein of human immunodeficiency virus and lipopolysaccharide induce expression of CD14 on human monocytes through differential utilization of interleukin-10.
We investigated the expression of membrane-bound CD14 (mCD14) on monocytes and soluble CD14 (sCD14) released into the culture supernatants of peripheral blood lymphocytes (PBMC) from human immunodeficiency virus (HIV)-infected individuals. Monocytes from HIV-positive individuals exhibited both enhanced mCD14 expression and sCD14 production in the PBMC culture supernatants compared to the levels of mCD14 and sCD14 in HIV-negative individuals. This enhanced mCD14 expression and sCD14 production in HIV-infected individuals may be due to the effects of cytokines, the bacterial product lipopolysaccharide (LPS), and/or the HIV regulatory antigens Tat and Nef. Interleukin-10 (IL-10), an immunoregulatory cytokine, as well as LPS enhanced mCD14 expression and the release of sCD14 in the culture supernatants. HIV-Nef, unlike Tat, enhanced mCD14 expression on monocytes but did not induce the release of sCD14 into the culture supernatants. Studies conducted to investigate the mechanism underlying HIV-Nef-induced mCD14 expression revealed that HIV-Nef upregulated mCD14 expression via a mechanism that does not involve endogenously produced IL-10. In contrast, LPS upregulated the expression of mCD14 and increased the release of sCD14 via a mechanism that involves, at least in part, endogenously produced IL-10. Furthermore, dexamethasone, an anti-inflammatory and immunosuppressive agent, inhibited HIV-Nef-induced CD14 expression in an IL-10-independent manner. In contrast, dexamethasone inhibited IL-10-dependent LPS-induced CD14 expression by interfering with IL-10-induced signals but not by blocking IL-10 production. These results suggest that HIV-Nef and IL-10 constitute biologically important modulators of CD14 expression which may influence immunobiological responses to bacterial infections in HIV disease.
Creery
David
D
Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Angel
Jonathan B
JB
Aucoin
Susan
S
Weiss
William
W
Cameron
William D
WD
Diaz-Mitoma
Francisco
F
Kumar
Ashok
A
D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology; D015693:Gene Products, nef / Q000494:pharmacology*; D006678:HIV / Q000737:chemistry*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D054311:nef Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D003907:Dexamethasone