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Tumor necrosis factor alpha and prostaglandin E2 production by human monocyte-derived macrophages infected with
1Virology Unit, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Abstract:
Infection of macrophages by intracellular parasites might modulate production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which, in turn, might have a profound effect on the outcome of the infection in vivo. In this study we examined in an in vitro system, the rickettsial yield in human monocyte-derived macrophages (MdM) and the PGE2 and TNF production by MdM infected with Rickettsia conorii RC, Casablanca strain) or Israeli spotted fever (ISF, G-212 strain). TNF and PGE2 were determined in the media of MdM infected with RC or ISF. TNF reached maximum levels 24 h post-infection and then declined, while PGE2 levels increased continuously during the infection up to 96 h post-infection. Addition of dexamethasone inhibited both TNF and PGE2 production and enhanced rickettsial yield in MdM. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF from rickettsial-infected MdM, while addition of PGE2 caused partial inhibition of TNF production from infected MdM.
Insights
Rickettsia conorii infection modulates macrophage production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2). Dexamethasone and indomethacin treatments altered these inflammatory responses and rickettsial growth in vitro.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Macrophages play a critical role in host defense against intracellular pathogens.
- Tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) are key inflammatory mediators that can influence infection outcomes.
- Rickettsial infections, such as those caused by Rickettsia conorii, pose significant public health challenges.
Purpose of the Study:
- To investigate the impact of Rickettsia conorii infection on human monocyte-derived macrophages (MdM).
- To quantify the production of TNF and PGE2 by MdM following infection with Rickettsia conorii strains.
- To explore the effects of dexamethasone and indomethacin on rickettsial yield and inflammatory mediator production.
Main Methods:
- Human monocyte-derived macrophages (MdM) were infected in vitro with Rickettsia conorii (RC) or Israeli spotted fever (ISF) strains.
- Tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) levels in the culture media were measured over time.
- The effects of dexamethasone and indomethacin on rickettsial yield and mediator production were assessed.
Main Results:
- TNF levels peaked at 24 hours post-infection and subsequently declined.
- PGE2 levels showed a continuous increase throughout the 96-hour infection period.
- Dexamethasone treatment inhibited both TNF and PGE2 production, leading to increased rickettsial yield.
- Indomethacin (PGE2 inhibitor) enhanced TNF production, while exogenous PGE2 partially inhibited TNF production.
Conclusions:
- Rickettsia conorii infection dynamically modulates TNF and PGE2 production in macrophages.
- The interplay between TNF and PGE2 influences the control of rickettsial replication within macrophages.
- Modulating these inflammatory pathways could represent a therapeutic strategy for rickettsial infections.