Impaired antigen presentation by human monocytes during endotoxin tolerance

Area of Science:

• Immunology
• Cellular Biology

Background:

• Endotoxin tolerance (ET) is a temporary hypo-responsiveness of monocytic cells to lipopolysaccharide (LPS).
• Monocytes are crucial antigen-presenting cells for initiating adaptive immune responses.
• ET can lead to immunoparalysis observed in critical illness.

Purpose of the Study:

• To investigate the impact of endotoxin tolerance on human monocyte's capacity to stimulate T-cells.
• To analyze changes in monocyte surface molecule expression during ET.
• To determine the role of cytokines like IL-10 and TGF-beta in ET-induced T-cell hypo-responsiveness.

Main Methods:

• Flow cytometry was used to analyze monocyte surface molecule expression (MHC class II, CD86, CD58, CD40, CD54, CD80).
• Peripheral blood mononuclear cells were primed in vitro with LPS to induce ET.
• T-cell stimulation assays were performed using recall antigens to assess T-cell proliferation and interferon-gamma (IFN-γ) production.

Main Results:

• LPS priming down-regulated major histocompatibility complex class II and CD86 on monocytes, dependent on IL-10.
• Other accessory molecules showed varied changes, with CD54 and CD80 remaining upregulated.
• ET resulted in diminished T-cell proliferation and IFN-γ release in response to recall antigens.
• Neutralizing IL-10 partially restored IFN-γ production but not T-cell proliferation.

Conclusions:

• Endotoxin tolerance impairs monocyte-mediated T-cell stimulation.
• IL-10 plays a significant role in the reduced IFN-γ production during ET.
• ET serves as a relevant model for understanding immunoparalysis in sepsis, trauma, and post-surgery patients.