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Published on: February 16, 2024
Small ruminant macrophage polarization may play a pivotal role on lentiviral infection
Helena Crespo1, Luigi Bertolotti, Magda Juganaru
1Instituto de Agrobiotecnología, CSIC-Universidad Pública de Navarra, Mutilva Baja, Navarra, Spain. ramses.reina@unavarra.es.
Abstract:
Small ruminant lentiviruses (SRLV) infect the monocyte/macrophage lineage inducing a long-lasting infection affecting body condition, production and welfare of sheep and goats all over the world. Macrophages play a pivotal role on the host's innate and adaptative immune responses against parasites by becoming differentially activated. Macrophage heterogeneity can tentatively be classified into classically differentiated macrophages (M1) through stimulation with IFN-γ displaying an inflammatory profile, or can be alternatively differentiated by stimulation with IL-4/IL-13 into M2 macrophages with homeostatic functions. Since infection by SRLV can modulate macrophage functions we explored here whether ovine and caprine macrophages can be segregated into M1 and M2 populations and whether this differential polarization represents differential susceptibility to SRLV infection. We found that like in human and mouse systems, ovine and caprine macrophages can be differentiated with particular stimuli into M1/M2 subpopulations displaying specific markers. In addition, small ruminant macrophages are plastic since M1 differentiated macrophages can express M2 markers when the stimulus changes from IFN-γ to IL-4. SRLV replication was restricted in M1 macrophages and increased in M2 differentiated macrophages respectively according to viral production. Identification of the infection pathways in macrophage populations may provide new targets for eliciting appropriate immune responses against SRLV infection.
Insights
Small ruminant lentiviruses (SRLV) infect macrophages, impacting sheep and goat health. Research shows M1 macrophages resist SRLV, while M2 macrophages support viral replication, offering potential new therapeutic targets.
Area of Science:
- Veterinary Immunology
- Infectious Diseases
- Cell Biology
Background:
- Small ruminant lentiviruses (SRLV) cause chronic infections in sheep and goats, affecting animal welfare and production.
- Macrophages are crucial immune cells that can adopt different activation states (M1 and M2) with distinct functions.
- SRLV infection is known to modulate macrophage functions, but the impact of macrophage polarization on susceptibility is unclear.
Purpose of the Study:
- To investigate if ovine and caprine macrophages can be differentiated into M1 and M2 populations.
- To determine if macrophage polarization influences susceptibility to SRLV infection.
- To identify potential pathways for controlling SRLV infection by targeting macrophage populations.
Main Methods:
- Ovine and caprine macrophages were stimulated with interferon-gamma (IFN-γ) to induce M1 polarization and with interleukin-4/13 (IL-4/13) for M2 polarization.
- Macrophage populations were characterized using specific markers.
- Viral replication of SRLV was quantified in M1 and M2 polarized macrophages.
Main Results:
- Ovine and caprine macrophages successfully differentiated into M1 and M2 subpopulations, expressing characteristic markers.
- M1 macrophages demonstrated restricted SRLV replication, while M2 macrophages showed increased viral production.
- Ovine macrophages exhibited plasticity, with M1 cells acquiring M2 markers upon stimulus change.
Conclusions:
- Macrophage polarization significantly impacts SRLV replication, with M1 macrophages being less permissive than M2 macrophages.
- Understanding SRLV-macrophage interactions in different polarization states is key to developing targeted interventions.
- This study provides insights into potential new strategies for controlling SRLV infections by manipulating macrophage immune responses.
