BACKGROUND: While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CXC family, in HIV-infected patients. MATERIALS AND METHODS: We examined serum levels of CXCL16 in clinically well-defined subgroups of HIV-infected individuals both before (n = 62) and during HAART (n = 40) as well as in age- and sex-matched healthy controls (n = 30). We also examined the effects of CXCL16 on inflammatory and anti-inflammatory cytokines and HIV replication in peripheral blood mononuclear cells (PBMC). RESULTS: Our main and novel findings were: (i) HIV-infected patients had significant raised CXCL16 levels according to disease severity and progression. (ii) During HAART, the immunological improvement was accompanied by a modest increase in CXCL16 level. (iii) While soluble CXCL16 promoted an anti-inflammatory response in PBMC from those on successful HAART, it induced an inflammatory response and enhanced HIV replication in PBMC from those with high viral load irrespectively of ongoing HAART. (iv) Recombinant HIV-tat protein significantly increased CXCL16 release in THP-1 macrophages. CONCLUSIONS: Our findings suggest a complex interaction between CXCL16 and HIV, promoting both inflammatory and anti-inflammatory effects as well as HIV replication, partly dependent on accompanying HIV replication.
BACKGROUND: While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CXC family, in HIV-infectedpatients. MATERIALS AND METHODS: We examined serum levels of CXCL16 in clinically well-defined subgroups of HIV-infected individuals both before (n = 62) and during HAART (n = 40) as well as in age- and sex-matched healthy controls (n = 30). We also examined the effects of CXCL16 on inflammatory and anti-inflammatory cytokines and HIV replication in peripheral blood mononuclear cells (PBMC). RESULTS: Our main and novel findings were: (i) HIV-infectedpatients had significant raised CXCL16 levels according to disease severity and progression. (ii) During HAART, the immunological improvement was accompanied by a modest increase in CXCL16 level. (iii) While soluble CXCL16 promoted an anti-inflammatory response in PBMC from those on successful HAART, it induced an inflammatory response and enhanced HIV replication in PBMC from those with high viral load irrespectively of ongoing HAART. (iv) Recombinant HIV-tat protein significantly increased CXCL16 release in THP-1 macrophages. CONCLUSIONS: Our findings suggest a complex interaction between CXCL16 and HIV, promoting both inflammatory and anti-inflammatory effects as well as HIV replication, partly dependent on accompanying HIV replication.
Authors: Sophie Limou; Cédric Coulonges; Joshua T Herbeck; Daniëlle van Manen; Ping An; Sigrid Le Clerc; Olivier Delaneau; Gora Diop; Lieng Taing; Matthieu Montes; Angélique B van't Wout; Geoffrey S Gottlieb; Amu Therwath; Christine Rouzioux; Jean-François Delfraissy; Jean-Daniel Lelièvre; Yves Lévy; Serge Hercberg; Christian Dina; John Phair; Sharyne Donfield; James J Goedert; Susan Buchbinder; Jérôme Estaquier; François Schächter; Ivo Gut; Philippe Froguel; James I Mullins; Hanneke Schuitemaker; Cheryl Winkler; Jean-François Zagury Journal: J Infect Dis Date: 2010-09-15 Impact factor: 5.226
Authors: Yun Young Go; Ernest Bailey; Deborah G Cook; Stephen J Coleman; James N Macleod; Kuey-Chu Chen; Peter J Timoney; Udeni B R Balasuriya Journal: J Virol Date: 2011-10-12 Impact factor: 5.103
Authors: Sanjay Sarkar; Lakshman Chelvarajan; Yun Young Go; Frank Cook; Sergey Artiushin; Shankar Mondal; Kelsi Anderson; John Eberth; Peter J Timoney; Theodore S Kalbfleisch; Ernest Bailey; Udeni B R Balasuriya Journal: J Virol Date: 2016-01-13 Impact factor: 5.103
Authors: Sanjay Sarkar; Ernest Bailey; Yun Young Go; R Frank Cook; Ted Kalbfleisch; John Eberth; R Lakshman Chelvarajan; Kathleen M Shuck; Sergey Artiushin; Peter J Timoney; Udeni B R Balasuriya Journal: PLoS Genet Date: 2016-12-08 Impact factor: 5.917