Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis

Ding, Andrew K.; Wallis, Zoey K.; White, Kevin S.; Sumer, Cinar Efe; Kim, Woong-Ki; Ardeshir, Amir; Williams, Kenneth C.

doi:10.1089/aid.2024.0008

Cited by 2 publications

(1 citation statement)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that increased microbial translocation as measured by LPS and sCD14 is characteristic of HIV infection even with suppressed viral replication and has been associated with cardiometabolic risk factors [48-50], it is likely a major driver of inflammatory monocyte activation. Further, in the SIV-macaque model of HIV-associated CVD and HIV-associated neurocognitive disorder (HAND), plasma IL-18, besides galectin-3 and galectin-9, was shown to correlate strongly with monocyte activation and turnover [51]. We believe that if the duration of SIV+ART was continued for more than a year in macaques, significant associations with inflammatory monocyte activation would be observed particularly in gut and cardiovascular tissues.…”

Section: Discussionmentioning

confidence: 99%

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy

Thirugnanam,

Wang,

Zheng

et al. 2024

Preprint

View full text Add to dashboard Cite

HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of HIV infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption and CVD pathogenesis. Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for biomarkers of intestinal epithelial barrier disruption (IEBD), inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). Higher plasma levels of IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP), during the chronic phase of treated SIV infection. Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10-12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV+ART phase along with a trend of increase in frequencies of activated CD14+CD16+intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could accelerate CVD pathogenesis. Further research is needed to understand mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated CVD and metabolic complications, enabling targeted interventions in people with HIV.

show abstract

Section: Discussionmentioning

confidence: 99%

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy

Thirugnanam,

Wang,

Zheng

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

The Association between IL-1β and IL-18 Levels, Gut Barrier Disruption, and Monocyte Activation during Chronic Simian Immunodeficiency Virus Infection and Long-Term Suppressive Antiretroviral Therapy

Thirugnanam,

Wang,

Zheng

et al. 2024

IJMS

View full text Add to dashboard Cite

HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of Human Immunodeficiency Virus (HIV) infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption (IEBD). Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for IEBD biomarkers, inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). During the chronic phase of treated SIV infection, elevated levels of plasma IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP). Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10 and 12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV + ART phase along with a trend of increase in the frequencies of activated CD14+CD16+ intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could fuel metabolic syndrome. Further research is needed to understand the mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated metabolic complications, enabling targeted interventions in people with HIV.

show abstract

Galectin-3, Galectin-9, and Interleukin-18 Are Associated with Monocyte/Macrophage Activation and Turnover More so than Simian Immunodeficiency Virus-Associated Cardiac Pathology or Encephalitis

Cited by 2 publications

References 60 publications

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy

The Association between IL-1β and IL-18 Levels, Gut Barrier Disruption, and Monocyte Activation during Chronic Simian Immunodeficiency Virus Infection and Long-Term Suppressive Antiretroviral Therapy

Contact Info

Product

Resources

About