Cytokine receptor signalling in neonatal macrophages: defective STAT-1 phosphorylation in response to stimulation with IFN-gamma
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1Department of Infectology and Paediatric Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. lmarodi@jaguar.dote.hu
Abstract:
We reported earlier that neonatal monocyte-derived macrophages (MDM) could not be fully activated with IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells. In this study we explored elements of IFN-gamma R-mediated signalling in cord monocytes and MDM. Intracellular expression of STAT-1 was analysed by flow cytometry. We have assessed phosphorylation of STAT-1 by using MoAbs that distinguish native and phosphorylated forms of STAT-1 on a discrete cell basis. Using MoAbs against the native form of STAT-1 revealed comparable expression of this protein in cord and adult cells (both monocytes and MDM). However, STAT-1 phosphorylation in response to IFN-gamma was significantly decreased in neonatal monocytes (P < 0.05) and MDM (P < 0.01) compared to adult cells (n > 5 for each). These data suggest deficient cytokine-receptor signalling in neonatal mononuclear phagocytes exposed to IFN-gamma. We propose that decreased STAT-1 phosphorylation and activation may represent developmental immaturity and may contribute to the unique susceptibility of neonates to infections by intracellular pathogens.
Insights
Neonatal monocytes and macrophages show impaired signaling in response to interferon-gamma (IFN-γ). This decreased STAT-1 phosphorylation suggests developmental immaturity, potentially explaining neonates' susceptibility to intracellular infections.
Area of Science:
- Immunology
- Neonatal Biology
- Cellular Signaling
Background:
- Neonatal monocyte-derived macrophages (MDM) exhibit incomplete activation by IFN-γ.
- This reduced responsiveness is not due to lower IFN-γ receptor expression.
Purpose of the Study:
- To investigate the mechanisms of IFN-γ receptor-mediated signaling in neonatal cord monocytes and MDM.
- To analyze STAT-1 expression and phosphorylation in response to IFN-γ in neonatal and adult cells.
Main Methods:
- Flow cytometry was used to analyze intracellular STAT-1 expression.
- Monoclonal antibodies (MoAbs) distinguishing native and phosphorylated STAT-1 were employed.
- STAT-1 phosphorylation was assessed in cord and adult monocytes and MDM after IFN-γ stimulation.
Main Results:
- STAT-1 expression was comparable in neonatal and adult monocytes and MDM.
- STAT-1 phosphorylation in response to IFN-γ was significantly decreased in neonatal monocytes (P < 0.05) and MDM (P < 0.01) compared to adult cells.
- These findings indicate deficient IFN-γ-mediated signaling in neonatal mononuclear phagocytes.
Conclusions:
- Decreased STAT-1 phosphorylation suggests developmental immaturity in neonatal immune cells.
- This signaling defect may contribute to increased neonatal susceptibility to intracellular pathogens.
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