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Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness
A Piani1, J P Hossle, T Birchler
1Division of Immunology, Hematology, Infectiology and Oncology, Zurich University Children's Hospital, Zürich, Switzerland.
Abstract:
Activation of phagocytes by lipopolysaccharide (LPS) causes synthesis and secretion of various mediators of inflammation. CD14, a glycosylphosphatidylinositol-anchored monocytic antigen serving as receptor for LPS, and members of the family of Toll-like receptors mediate cellular activation in response to LPS. Here we investigated whether expression of MHC class II molecules modified the response to LPS. Comparing LPS responsiveness of human and murine cells differing for expression of MHC class II molecules, we found that lack or a low level of expression of MHC class II molecules resulted in diminished secretion of pro-inflammatory cytokines following stimulation with LPS. Thus, expression of MHC class II molecules modifies LPS responsiveness, a finding suggesting that these molecules contribute to the pathogenesis not only of exotoxin-triggered toxic shock but also of endotoxin-triggered septic shock. Additionally to their role in antigen-specific immunity MHC class II molecules may influence the inflammatory response triggered by microbial constituents.
Insights
MHC class II molecules enhance the inflammatory response to lipopolysaccharide (LPS). Reduced expression of these molecules leads to diminished pro-inflammatory cytokine secretion, impacting conditions like septic shock.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Medicine
Background:
- Phagocyte activation by lipopolysaccharide (LPS) triggers the release of inflammatory mediators.
- CD14 and Toll-like receptors are key mediators of cellular activation by LPS.
- The role of MHC class II molecules in LPS responsiveness is not fully understood.
Purpose of the Study:
- To investigate whether MHC class II molecule expression influences cellular responses to LPS.
- To determine the impact of varying MHC class II expression levels on pro-inflammatory cytokine secretion.
Main Methods:
- Comparative analysis of LPS responsiveness in human and murine cells with differing MHC class II expression.
- Quantification of pro-inflammatory cytokine secretion following LPS stimulation.
Main Results:
- Cells with absent or low MHC class II expression exhibited diminished pro-inflammatory cytokine secretion upon LPS stimulation.
- MHC class II expression significantly modifies cellular responsiveness to LPS.
Conclusions:
- MHC class II molecules play a crucial role in modulating the inflammatory response to LPS.
- These findings suggest MHC class II molecules contribute to the pathogenesis of septic shock.
- Beyond antigen-specific immunity, MHC class II molecules influence inflammatory responses to microbial components.