Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa - PubMed (original) (raw)

. 2009 Apr 21;106(16):6718-23.

doi: 10.1073/pnas.0901983106. Epub 2009 Apr 8.

Djeneba Dabitao, Jay H Bream, Blake Charvat, Oliver Laeyendecker, Noah Kiwanuka, Tom Lutalo, Godfrey Kigozi, Aaron A R Tobian, Jordyn Gamiel, Jessica D Neal, Amy E Oliver, Joseph B Margolick, Nelson Sewankambo, Steven J Reynolds, Maria J Wawer, David Serwadda, Ronald H Gray, Thomas C Quinn

Affiliations

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Andrew D Redd et al. Proc Natl Acad Sci U S A. 2009.

Abstract

Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon's role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1.

Fig. 1.

Baseline microbial markers and circulating cytokine levels of uninfected U.S. and African subjects. Differences between HIV-negative U.S. subjects (n = 24) and uninfected African subjects in baseline serum levels (n = 86) of LPS (A), LBP (B), EndoCAb (C), sCD14 (D), GM-CSF (E), IFN-γ (F), IL-8 (G), IL-2 (H), and TNF-α (I) were examined using the Mann-Whitney rank-sum test. The results are shown with significance indicated where applicable (P < .05).

Fig. 2.

Fig. 2.

Longitudinal changes of microbial translocation markers according to African disease progression groups. The last HIV-negative time point for each patient (year 0) and all subsequent years postseroconversion are shown for each progression group [LTNP (circles), SP (inverted triangles), and RP (squares)] for LPS (A), EndoCAb (B), LBP (C), and sCD14 (D). Longitudinal variation in patient levels was determined using linear multilevel modeling fit with slopes in the log scale for each group. The resulting regression line for each group is shown in the respective color. Significant inequality in slopes across groups is indicated where applicable (P < .05).

Fig. 3.

Fig. 3.

African subject-specific microbial translocation markers according to progression group. Levels of microbial translocation marker levels are shown for the LTNP, SP, and RP groups for LPS (A–C), EndoCAb (D–F), LBP (G–I), and sCD14 (J–L). Linear multilevel modeling fit slopes in the log scale of each group are shown with the 95% CI on each graph, with significance noted by an asterisk (P < .05). Patient-specific color-coding is consistent throughout multiple assays within the denoted progression group (

Fig. S2

).

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