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Microbial translocation in simian immunodeficiency virus (SIV)-infected rhesus monkeys (Macaca mulatta)
C Leinert1, C Stahl-Hennig, A Ecker
1German Primate Center, Infection Biology Unit, Kellnerweg, Göttingen, Germany.
Background:
Chronic immune activation is a hallmark of HIV infection and has been postulated as major factor in the pathogenesis of AIDS. Recent evidence suggests that activation of immune cells is triggered by microbial translocation through the impaired gastrointestinal barrier.
Methods:
To determine the association between microbial translocation and disease progression, we have retrospectively analyzed microbial products, viral load and markers of immune activation in a cohort of 37 simian immunodeficiency virus-infected rhesus monkeys, divided in two groups with distinct disease courses.
Results:
As seen in HIV-infected patients, we found elevated levels of lipopolysaccharide (LPS) in infected animals. However, LPS levels or LPS control mechanisms like endotoxin core antibodies or LPS-binding protein did not differ between groups with different disease progression. In contrast, neopterin, a metabolic product of activated macrophages, was higher in fast progressors than in slow progressors.
Conclusion:
Our data indicate that translocation of microbial products is not the major driving force of immune activation in HIV infection.
Insights
Microbial translocation is not the primary driver of immune activation in HIV infection. While lipopolysaccharide (LPS) levels were elevated, neopterin, a marker of macrophage activation, correlated with disease progression.
Area of Science:
- Immunology
- Virology
- Pathogenesis of infectious diseases
Background:
- Chronic immune activation is a key feature of Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) pathogenesis.
- Immune cell activation is increasingly linked to microbial translocation across a compromised gastrointestinal barrier.
Purpose of the Study:
- To investigate the association between microbial translocation and disease progression in Simian Immunodeficiency Virus (SIV) infection.
- To evaluate the role of microbial products and immune activation markers in distinct disease courses.
Main Methods:
- Retrospective analysis of a cohort of 37 SIV-infected rhesus monkeys.
- Measurement of microbial products (e.g., lipopolysaccharide - LPS), viral load, and immune activation markers (e.g., neopterin, endotoxin core antibodies, LPS-binding protein).
- Comparison between groups with differing disease progression rates.
Main Results:
- Elevated lipopolysaccharide (LPS) levels were observed in SIV-infected animals, similar to HIV-infected patients.
- LPS levels and control mechanisms (endotoxin core antibodies, LPS-binding protein) did not differ between fast and slow progressors.
- Neopterin levels, a marker of activated macrophages, were significantly higher in fast progressors compared to slow progressors.
Conclusions:
- Microbial translocation, indicated by LPS levels, does not appear to be the principal driver of immune activation in HIV infection.
- Neopterin levels, reflecting macrophage activation, show a stronger association with disease progression than microbial translocation markers.
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