Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV

Abstract

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of b-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann-Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventysix participants were included (128 HIV+ and 48 HIV-); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm 3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.

Changes in the Fungal Marker β-D-Glucan After Antiretroviral Therapy and Association With Adiposity

“…Similarly to LPS, BDG has been associated with inflammation and immune activation in PWH [12, 29, 32, 39, 40]. Contrary to previous reports, we failed to observe any association between BDG and markers of monocyte, T-cell activation, or systemic inflammation at any time point.…”

“…Markers such as β-D-glucan (BDG), a polysaccharide cell wall component of most fungal species, is known to be highly immunogenic, stimulating macrophages, neutrophils, and T cells and leading to release of pro-inflammatory cytokines such as interleukin (IL)-8 and tumor necrosis factor α [10, 11]. We have previously observed that markers of fungal translocation are associated with immune activation and systemic inflammation in virally suppressed PWH [12].…”

Fungal Translocation: A Driving Force Behind the Occurrence of Non-AIDS Events?

“…The results reported by Mehraj et al complement the findings of that case-control study by identifying early ART as an effective intervention to cease the increase of βDG levels. The findings by Mehraj et al can be also seen as being in line with findings from other recent studies in which it was found that circulating βDG levels in PLWH on ART correlated with other markers of immune activation [12,13], systemic inflammation [13,14], and microbial translocation, including Lactobacillales proportions in the gut microbiome [6], and that elevated βDG levels were associated with neurocognitive and cardiovascular non-AIDS events [15,16].…”

Daily variations of gut microbial translocation markers in ART-treated HIV-infected people

“…Measurement of microbial translocation plasma markers have been frequently performed in studies evaluating therapeutic interventions and assessing the risk of developing non-AIDS co-morbidities [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Circulating levels of lipopolysaccharide (LPS) are commonly measured to assess the level of bacterial translocation.…”