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CRIg Functions as a Macrophage Pattern Recognition Receptor to Directly Bind and Capture Blood-Borne Gram-Positive
Zhutian Zeng1, Bas G J Surewaard2, Connie H Y Wong1
1The Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Abstract:
Kupffer cells (KCs), the vast pool of intravascular macrophages in the liver, help to clear blood-borne pathogens. The mechanisms by which KCs capture circulating pathogens remain unknown. Here we use intra-vital imaging of mice infected with Staphylococcus aureus to directly visualize the dynamic process of bacterial capture in the liver. Circulating S. aureus were captured by KCs in a manner dependent on the macrophage complement receptor CRIg, but the process was independent of complement. CRIg bound Staphylococcus aureus specifically through recognition of lipoteichoic acid (LTA), but not cell-wall-anchored surface proteins or peptidoglycan. Blocking the recognition between CRIg and LTA in vivo diminished the bacterial capture in liver and led to systemic bacterial dissemination. All tested Gram-positive, but not Gram-negative, bacteria bound CRIg in a complement-independent manner. These findings reveal a pattern recognition role for CRIg in the direct capture of circulating Gram-positive bacteria from the bloodstream.
Insights
Kupffer cells capture Gram-positive bacteria via the complement receptor CRIg, which recognizes lipoteichoic acid. This direct interaction is crucial for preventing bacterial spread in the bloodstream.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Kupffer cells (KCs) are liver macrophages that clear blood-borne pathogens.
- The mechanisms of KC pathogen capture are not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which Kupffer cells capture circulating Staphylococcus aureus.
- To elucidate the role of the macrophage complement receptor CRIg in pathogen capture.
Main Methods:
- Intra-vital imaging in mice infected with Staphylococcus aureus.
- Assessment of bacterial capture dependence on complement and CRIg.
- In vivo blocking of CRIg-lipoteichoic acid interaction.
Main Results:
- Kupffer cells captured Staphylococcus aureus in a complement-independent manner, dependent on the macrophage complement receptor CRIg.
- CRIg specifically recognized lipoteichoic acid (LTA) on Gram-positive bacteria.
- Blocking CRIg-LTA interaction impaired bacterial capture and led to systemic dissemination.
Conclusions:
- CRIg mediates direct capture of circulating Gram-positive bacteria by Kupffer cells.
- CRIg acts as a pattern recognition receptor for LTA, crucial for innate immunity against Gram-positive bacteria.
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