Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection.
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, acute-phase proteins, inflammatory markers, and proinflammatory cytokines in individuals with (infected [INF]) or without (uninfected [UN]) S. stercoralis infections. Finally, we also measured the levels of all of these markers in INF individuals following treatment of S. stercoralis infection. We show that INF individuals exhibit significantly higher plasma levels of microbial translocation markers (LPS, soluble CD14 [sCD14], intestinal fatty acid-binding protein [iFABP], and endotoxin core IgG antibody [EndoCAb]), acute-phase proteins (α-2 macroglobulin [α-2M], C-reactive protein [CRP], haptoglobin, and serum amyloid protein A [SAA]), inflammatory markers (matrix metalloproteinase 1 [MMP-1] and heme oxygenase 1 [HO-1]), and proinflammatory cytokines (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], and IL-1β) than do UN individuals. INF individuals exhibit significantly decreased levels of tissue inhibitor of metalloproteinases 4 (TIMP-4). 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.
National Institute of Health-NIRT-International Center for Excellence in Research, Chennai, India anuradha@nirt.res.in.
Anuradha
A
Rajamanickam
National Institute of Health-NIRT-International Center for Excellence in Research, Chennai, India.
Saravanan
S
Munisankar
National Institute of Health-NIRT-International Center for Excellence in Research, Chennai, India.
Yukthi
Y
Bhootra
National Institute for Research in Tuberculosis, Chennai, India.
Chandrakumar
C
Dolla
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Thomas B
TB
Nutman
National Institute of Health-NIRT-International Center for Excellence in Research, Chennai, India.|Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Subash
S
Babu
D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000378:metabolism* / Q000382:microbiology; D000328:Adult; D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D017171:Strongyloides stercoralis / Q000378:metabolism* / Q000502:physiology*; D013322:Strongyloidiasis / Q000097:blood / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult
D000209:Acute-Phase Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D007074:Immunoglobulin G; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D002097:C-Reactive Protein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D020781:Matrix Metalloproteinase 1
Strongyloides stercoralis; acute-phase proteins; inflammatory markers; microbial translocation markers; proinflammatory cytokines