Co-existence of classical and alternative activation programs in macrophages responding to Toxoplasma gondii
Veerupaxagouda Patil1, Yanlin Zhao1, Suhagi Shah1
1Department of Medicine, Center for Immunity and Inflammation, Rutgers-New Jersey Medical School (NJMS), Newark, NJ 07101, USA.
Abstract:
Pro-inflammatory M1 macrophages are critical for defense against intracellular pathogens while alternatively-activated M2 macrophages mediate tissue homeostasis and repair. Whether these distinct activation programs are mutually exclusive or can co-exist within the same cell is unclear. Here, we report the co-existence of these programs in Toxoplasma gondii-elicited inflammatory macrophages. This is independent of parasite expression of the virulence factor ROP16 and host cell expression of signal transducer and activator of transcription 6 (STAT6). Furthermore, this observation was recapitulated by IFN-γ and IL-4 treated bone marrow-derived macrophages in vitro. These results highlight the multi-functionality of macrophages as they respond to diverse microbial and endogenous stimuli.
Insights
Macrophages can exhibit both pro-inflammatory (M1) and tissue-repairing (M2) functions simultaneously. This study demonstrates this dual capability in macrophages responding to Toxoplasma gondii infection and in vitro stimuli, revealing macrophage multi-functionality.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease
Background:
- Macrophages possess distinct M1 (pro-inflammatory) and M2 (tissue repair) activation states.
- It remains unclear if these M1 and M2 programs are mutually exclusive within a single macrophage.
Purpose of the Study:
- To investigate the co-existence of M1 and M2 activation programs within the same macrophage.
- To determine if this co-existence is dependent on specific parasite or host factors.
Main Methods:
- Analysis of Toxoplasma gondii-elicited inflammatory macrophages.
- Assessment of macrophage activation in vitro using interferon-gamma (IFN-γ) and interleukin-4 (IL-4).
- Evaluation of the role of parasite ROP16 and host STAT6 signaling.
Main Results:
- Macrophages elicited by Toxoplasma gondii exhibit co-existing M1 and M2 activation programs.
- This dual activation is independent of parasite ROP16 and host STAT6.
- Similar co-activation was observed in bone marrow-derived macrophages treated with IFN-γ and IL-4 in vitro.
Conclusions:
- Macrophages display multi-functional capabilities, integrating distinct activation programs.
- Macrophage plasticity allows for simultaneous M1 and M2 functions in response to diverse stimuli.
- This finding broadens the understanding of macrophage roles in immunity and tissue homeostasis.
