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The Effects of Pathogen-Associated Molecular Patterns on Peripheral Blood Monocytes in Patients with Non-alcoholic
Qian Li1,2, Julia D Rempel1,2, Jiaqi Yang1
1Section of Hepatology, University of Manitoba, Winnipeg, Manitoba, Canada.
Background:
Innate immune responses to gut-derived pathogen-associated molecular patterns (PAMPs) have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD patients have increased sensitivity to PAMP exposure has yet to be reported.
Methods:
Peripheral blood mononuclear cell (PBMC)/monocytes were exposed to lipopolysaccharide (LPS), Pam3CSK4, or BSA conjugated palmitate in vitro. Changes in toll-like receptors (TLR), cytokines, and chemokine receptors (CR) expressions were documented by flow cytometry and/or enzyme-linked immunoabsorbent assays (ELISAs).
Results:
TLR2 and TLR4 expression were similar at baseline and increased to a similar extent (TLR2) or remained unchanged (TLR4) following PAMP exposure in NAFLD and healthy control (HC) monocytes. Proinflammatory IL-1β and IL-6 levels were similar at baseline but increased in a concentration-dependent manner to a greater extent in NAFLD PBMCs. CCR1 and CCR2 expressions at baseline were similar and decreased to a similar extent in NAFLD and HC monocytes. The extent of PAMP-induced proinflammatory cytokine release correlated with evidence of hepatocyte injury (CK18M30 levels).
Discussion:
NAFLD patients have increased proinflammatory cytokine responses following exposure to PAMPs relative to HC subjects. This response is concentration-dependent and correlates with the extent of hepatic injury.
Insights
Nonalcoholic fatty liver disease (NAFLD) patients exhibit heightened inflammatory responses to pathogen-associated molecular patterns (PAMPs). This increased cytokine release in NAFLD correlates with liver injury severity.
Area of Science:
- Immunology
- Hepatology
- Gastroenterology
Background:
- Innate immune responses to gut-derived pathogen-associated molecular patterns (PAMPs) are linked to nonalcoholic fatty liver disease (NAFLD) pathogenesis.
- Previous research has not determined if NAFLD patients exhibit heightened sensitivity to PAMP exposure.
Purpose of the Study:
- To investigate the differential immune response to PAMPs in patients with NAFLD compared to healthy controls.
- To explore the correlation between PAMP-induced immune responses and markers of liver injury.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from NAFLD patients and healthy controls (HC) were stimulated with lipopolysaccharide (LPS), Pam3CSK4, and palmitate conjugates in vitro.
- Flow cytometry and ELISAs were used to quantify changes in toll-like receptor (TLR), cytokine, and chemokine receptor (CR) expression.
Main Results:
- NAFLD PBMCs showed significantly greater concentration-dependent increases in proinflammatory cytokines IL-1β and IL-6 compared to HC.
- TLR2 and TLR4 expression changes and CCR1/CCR2 expression following PAMP exposure were similar between NAFLD and HC monocytes.
- The magnitude of PAMP-induced proinflammatory cytokine release correlated with hepatocyte injury markers (CK18M30 levels).
Conclusions:
- NAFLD patients demonstrate an exaggerated proinflammatory cytokine response to PAMPs compared to healthy individuals.
- This heightened immune response is concentration-dependent and associated with the degree of liver injury in NAFLD.
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