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Lipopolysaccharide can block the potential of monocytes to differentiate into dendritic cells
K A Palucka1, N Taquet, F Sanchez-Chapuis
1ESA 7087 Université Paris 6-Centre Nationale de la Recherche Scientifique & Laboratoire d'Immunologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Hôpital Pitié-Salpêtrière, France.
Abstract:
We examined whether priming monocytes (MO) with lipopolysaccharide (LPS) influenced their further differentiation into either macrophages (Mphi) or dendritic cells (DC). LPS-primed MO differentiated into Mphi when cultured further with Mphi colony-stimulating factor (M-CSF) but, if cultured then with granulocyte/Mphi (GM)-CSF and IL-4 (interleukin-4), only about 30% of the cells differentiated into CD1a+ CD14- DC and half became CD1a- CD14+ Mphi. Cytokines present during LPS priming could affect subsequent MO differentiation. Relative to priming with LPS alone, adding M-CSF to LPS did not modify differentiation of MO to Mphi in further culture with M-CSF, nor did it change the way of differentiation of MO into DC was altered if culture was later switched to GM-CSF/IL-4. Using GM-CSF/IL-4 plus LPS upon priming did not modify differentiation of MO to Mphi in further culture with M-CSF, as compared to priming with GM-CSF/IL-4 alone, but it counteracted the effect of LPS on the differentiation of MO to DC in further culture with GM-CSF/IL-4: about 75% of cells then became DC. Alternatively, despite activation by LPS, mature M-CSF-induced Mphi preserved the potential to differentiate into DC on subsequent culture with GM-CSF/IL-4. Thus, LPS, a bacterial product known to sustain maturation of MO/Mphi as well as of DC, may block the differentiation of MO into DC, except if signal triggering DC differentiation is delivered concomitantly, and modulate in this manner the induction of adaptive immune responses to infection.
Insights
Lipopolysaccharide (LPS) priming influences monocyte (MO) differentiation. LPS can block dendritic cell (DC) development unless DC-inducing signals are present, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease Research
Background:
- Monocytes (MO) are crucial immune cells that differentiate into macrophages (Mphi) or dendritic cells (DC).
- Lipopolysaccharide (LPS) is a bacterial product known to activate and mature myeloid cells.
- The specific differentiation pathway of monocytes can be influenced by priming signals and subsequent culture conditions.
Purpose of the Study:
- To investigate how lipopolysaccharide (LPS) priming affects the subsequent differentiation of monocytes (MO) into macrophages (Mphi) or dendritic cells (DC).
- To determine the role of cytokines present during LPS priming on monocyte differentiation outcomes.
- To understand how LPS modulates the potential of monocytes and macrophages to differentiate into dendritic cells.
Main Methods:
- Monocytes (MO) were primed with lipopolysaccharide (LPS) alone or in combination with specific cytokines (M-CSF, GM-CSF, IL-4).
- Primed cells were subsequently cultured with differentiation-inducing factors (M-CSF for Mphi, GM-CSF/IL-4 for DC).
- Flow cytometry was used to analyze the expression of cell surface markers (CD1a, CD14) to identify differentiated Mphi and DC populations.
Main Results:
- LPS-primed monocytes differentiated into Mphi when cultured with M-CSF.
- When cultured with GM-CSF/IL-4, LPS-primed monocytes showed reduced differentiation into DC (approx. 30%) and increased Mphi differentiation (approx. 50%).
- Priming with GM-CSF/IL-4 and LPS enhanced DC differentiation to approx. 75% when subsequently cultured with GM-CSF/IL-4, indicating LPS can block DC differentiation unless DC-inducing signals are co-delivered.
Conclusions:
- Lipopolysaccharide (LPS) can inhibit monocyte (MO) differentiation into dendritic cells (DC) under certain conditions.
- The presence of specific cytokines during LPS priming critically influences the subsequent differentiation of MO into Mphi or DC.
- Mature M-CSF-induced Mphi retain the capacity to differentiate into DC upon subsequent stimulation with GM-CSF/IL-4, suggesting plasticity.
- LPS's modulation of monocyte differentiation pathways can significantly impact adaptive immune responses during infection.