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Updated: Jun 28, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Myeloid differentiation protein-2-dependent and -independent neutrophil accumulation during Escherichia coli
Shanshan Cai1, Rachel L Zemans, Scott K Young
1Laboratory of Lung Biology, Department of Pathobiological Sciences and Center for Experimental Infectious Disease Research, Louisiana State University (LSU), Baton Rouge, Louisiana 70803, USA.
Abstract:
Bacterial pneumonia remains a serious disease. Pattern recognition receptors play an integral role in neutrophil accumulation during pneumonia. Although myeloid differentiation protein (MD)-2 has been recognized as a key molecule for LPS signaling, the role of MD-2 in neutrophil accumulation in the lung during bacterial infection has not been explored. Here, we investigate the role of MD-2 in Escherichia coli LPS-induced lung inflammation and E. coli-induced pneumonia. LPS-induced CD14-independent neutrophil accumulation was abolished in CD14/MD-2(-/-) mice. MD-2(-/-) mice challenged with LPS displayed attenuated neutrophil influx, NF-kappaB activation, cytokine/chemokine expression, and lung histopathology. MD-2(-/-) mice transplanted with MD-2(+/+) bone marrow demonstrated decreased neutrophil influx and cytokine/chemokine expression in the lungs when challenged by LPS. MD-2(-/-) mice infected with E. coli demonstrated reduced neutrophil influx and cytokine/chemokine expression in the lungs, whereas heat-killed E. coli did not induce either neutrophil accumulation or cytokine/chemokine expression in MD-2(-/-) mice infected with E. coli. Furthermore, MD-2(-/-) mice displayed increased bacterial burden in the lungs and enhanced bacterial dissemination. Toll-like receptor (TLR)-5(-/-) mice infected with E. coli exhibited attenuated neutrophil accumulation, whereas MD-2/TLR5(-/-) mice inoculated with E. coli showed further attenuated neutrophil influx and impaired bacterial clearance. Taken together, these new findings demonstrate: (1) the important role of MD-2 in the CD14-independent LPS-mediated cascade of neutrophil influx; (2) the relative importance of bone marrow- and non-bone marrow cell-derived MD-2 in LPS-induced inflammation; and (3) the essential role of MD-2-dependent and MD-2-independent (TLR5) signaling in E. coli-induced neutrophil accumulation and pulmonary host defense.
Insights
Myeloid differentiation protein (MD)-2 is crucial for neutrophil recruitment in bacterial pneumonia. MD-2 deficiency impairs host defense against E. coli, increasing bacterial burden and dissemination.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Bacterial pneumonia poses a significant health threat.
- Pattern recognition receptors are vital for neutrophil response in pneumonia.
- Myeloid differentiation protein (MD)-2 is known for LPS signaling but its role in bacterial pneumonia is unclear.
Purpose of the Study:
- To investigate the role of MD-2 in Escherichia coli LPS-induced lung inflammation.
- To examine the function of MD-2 in E. coli-induced pneumonia and host defense.
Main Methods:
- Utilized CD14/MD-2(-/-) and MD-2(-/-) mice models.
- Administered E. coli LPS and live/heat-killed E. coli for infection.
- Assessed neutrophil influx, NF-kappaB activation, cytokine/chemokine expression, and bacterial burden.
- Employed bone marrow transplantation experiments.
- Investigated Toll-like receptor (TLR)-5(-/-) and MD-2/TLR5(-/-) mice.
Main Results:
- MD-2 deficiency abolished LPS-induced CD14-independent neutrophil accumulation.
- MD-2(-/-) mice showed reduced inflammation and impaired host defense against E. coli infection.
- Bone marrow-derived MD-2 plays a significant role in LPS-induced inflammation.
- MD-2 and TLR5 signaling are essential for E. coli-induced neutrophil accumulation and bacterial clearance.
Conclusions:
- MD-2 is critical for CD14-independent LPS-mediated neutrophil influx.
- Both bone marrow-derived and non-bone marrow cell-derived MD-2 contribute to LPS-induced inflammation.
- MD-2-dependent and TLR5-dependent pathways are essential for pulmonary host defense against E. coli.
