Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

Abstract

Microbial translocation, characterized by elevated levels of lipopolysaccharide (LPS) and related markers, is a common occurrence in HIV and some parasitic infections. This is usually associated with extensive inflammation and immune activation. To examine the occurrence of microbial translocation and the associated inflammatory response in asymptomatic Strongyloides stercoralis infection, we measured the plasma levels of LPS and other microbial translocation markers, acutephase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF] . Following treatment of S. stercoralis infection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show that S. stercoralis infection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation is a feature of asymptomatic S. stercoralis infection and is associated with an inflammatory response.KEYWORDS microbial translocation markers, Strongyloides stercoralis, acute-phase proteins, inflammatory markers, proinflammatory cytokines M icrobial translocation refers to the process by which the translocation of bacterial products results in elevated levels of lipopolysaccharide (LPS) in the circulation without overt bacteremia (1). LPS and 16S rRNA (common to most bacteria) are often used as indicators of bacterial translocation, and endotoxin core IgG antibody (EndoCAb) is also used as a surrogate marker for the measurement of circulating LPS levels (1, 2). iFABP may also reflect a breach in epithelial integrity associated with chronic intestinal infections (3). The prevalence of increased acute-phase protein concentrations during episodes of inflammation is used as a supporting prognostic and diag-

Heme oxygenase-1 promoter (GT) n polymorphism associates with HIV neurocognitive impairment

“…A previous report associated short HO-1 (GT) n repeat lengths with lower plasma soluble CD14 (sCD14) levels in ARTtreated African American PLWH, but not in European American PLWH, which suggests that short HO-1 (GT) n alleles have a downmodulating effect against HIV-associated inflammation in African Americans. 8 We determined relationships between HO-1 (GT) n genotype, plasma sCD163 (monocyte activation), 26 and plasma sHO-1 (inflammation and oxidative stress) 27,28 in ART-treated, virally suppressed individuals within the cohort. We did not observe significant differences in the total cohort (not shown).…”

“…We do not have direct proof of this hypothesis, but we do find some evidence supporting this in the published literature. 27,28,49 Several reports of increased plasma sHO-1 levels in human disease states associated with systemic inflammation provide such evidence: acute HIV infection, 49 Strongyloides stercoralis infection, 28 and coronary artery disease. 27 A major implication of our study is that individuals of African ancestry might be more vulnerable to HIV NCI than individuals of European ancestry because of differences in HO-1 (GT) n allele genotype prevalence.…”

“…Further supporting a role for the HO-1 (GT) n allele genotype in HIV pathogenesis in individuals of African ancestry, we found associations between allele genotype, inflammatory and oxidative stress biomarkers, and HIV disease status. We assessed plasma soluble CD163 as a marker of inflammation and monocyte activation, 26 plasma sHO-1 as a marker of inflammation and oxidative stress, 27,28 and current CD4 + T-cell count (cutoff of 350 cells/μL) as a marker of HIV immune status. 31,32 We demonstrated that the presence of 1 or more short HO-1 (GT) n alleles associates with lower plasma sHO-1 in virally suppressed African American PLWH, but not in European American PLWH, with CD4 + T-cell counts greater than 350 cells/μL.…”

“…26 Plasma soluble HO-1 (sHO-1) serves as a marker of inflammation and oxidative stress. 27,28 Each was quantified in duplicate by commercial ELISA: (1) sCD163 (R & D Systems, #DY1607; LOD 156 pg/mL) and (2) sHO-1 (ENZO Life Sciences, #ADI-960-800; LOD 49 pg/mL) in stored, frozen (−80°C) plasma samples.…”

Helminth Mediated Attenuation of Systemic Inflammation and Microbial Translocation in Helminth-Diabetes Comorbidity

“…Our data reveal a novel association of diminished metabolic endotoxemia and intestinal permeability in the presence of Ss infection. Although, Ss infection by itself is known to promote microbial translocation (Rajamanickam et al, 2017 ), its influence in the presence of a diabetic environment appears to be one of downmodulation and this could be due to differential interaction of the helminth infection with the gut microbiota in the context of diabetes mellitus. More conclusive proof that Ss drives this downregulated microbial translocation comes from our data on the significant reversal of this downmodulated response following anthelmintic treatment.…”