View stunning SlideShares in full-screen with the new iOS app!Introducing SlideShare for AndroidExplore all your favorite topics in the SlideShare appGet the SlideShare app to Save for Later — even offline
View stunning SlideShares in full-screen with the new Android app!View stunning SlideShares in full-screen with the new iOS app!
Mayhem that occurs to mucosal surfaces after acute infection damages immunological and structural GI barrier allowing intestinal microbial products to cross over to the “other side”
Systemic microbes and microbial products stimulate the adaptive and innate immune systems and exacerbate immune activation
Evidence for Increased Gut Permeability Increased gut permeability in HIV + individuals Kotler, D.P., et al. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 421-8 1984. Batman, P. A., et al. HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda. Gut 43:350-5 1998. Griffin, G. E. Malabsorption, malnutrition and HIV disease. Baillieres Clin Gastroenterol 4:361-73 1990. Kapembwa, M. S., et al. Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects. Clin Sci (Lond) 81:327-34 1991. Miller, A. R., et al. Jejunal mucosal architecture and fat absorption in male homosexuals infected with human immunodeficiency virus. Q J Med 69:1009-19 1988.
LPS is an indicator of translocation of other immunostimulatory products
Does it correlate with other measures of (non-LPS) immune activation?
Plasma LPS levels correlate with marker of pDC activation Other immunostimulatory factors apart from LPS Plasma LPS levels correlate with degree of CD8 T cell activation Other factors directly or indirectly stimulating T cells
Markers of activation of innate and adaptive immunity correlate with LPS
Other bacterial and viral products are likely to be involved
Microbial translocation also occurs in elite controllers and this is associated with T cell activation and possibly slow CD4 T cell decline
HAART results in slightly reduced microbial translocation and CD4 reconstitution is limited by immune activation which is associated with microbial translocation
Microbial translocation is a cause of immune activation in HIV-infected individuals
Many Thanks To… VRC Daniel Douek David Price Tedi Asher Srinivas Rao Mario Roederer U. Minn Tim Schacker Ashley Haase CWRU Mike Lederman OHSU Louis Picker UCSF Peter Hunt Steve Deeks U. Penn Guido Silvestri Tulane Cristian Apetrei Ivona Pandreiou H. Bicere Olivier Lambotte