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The Properties of Proinflammatory Ly6Chi Monocytes Are Differentially Shaped by Parasitic and Bacterial Liver
Stefan Hoenow1, Karsten Yan2, Jill Noll1
1Department of Molecular Parasitology and Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
Abstract:
In the past, proinflammatory CD11b+Ly6Chi monocytes were predominantly considered as a uniform population. However, recent investigations suggests that this population is far more diverse than previously thought. For example, in mouse models of Entamoeba (E.) histolytica and Listeria (L.) monocytogenes liver infections, it was shown that their absence had opposite effects. In the former model, it ameliorated parasite-dependent liver injury, whereas in the listeria model it exacerbated liver pathology. Here, we analyzed Ly6Chi monocytes from the liver of both infection models at transcriptome, protein, and functional levels. Paralleled by E. histolytica- and L. monocytogenes-specific differences in recruitment-relevant chemokines, both infections induced accumulation of Ly6C+ monocytes at infection sites. Transcriptomic analysis revealed a high similarity between monocytes from naïve and parasite-infected mice and a clear proinflammatory phenotype of listeria-induced monocytes. This was further reflected by the upregulation of M2-related transcription factors (e.g., Mafb, Nr4a1, Fos) and higher CD14 expression by Ly6Chi monocytes in the E. histolytica infection model. In contrast, monocytes from the listeria infection model expressed M1-related transcription factors (e.g., Irf2, Mndal, Ifi204) and showed higher expression of CD38, CD74, and CD86, as well as higher ROS production. Taken together, proinflammatory Ly6Chi monocytes vary considerably depending on the causative pathogen. By using markers identified in the study, Ly6Chi monocytes can be further subdivided into different populations.
Insights
Proinflammatory monocytes (CD11b+Ly6Chi) are diverse. Their function differs in Entamoeba histolytica and Listeria monocytogenes liver infections, revealing distinct molecular signatures and enabling further population subdivision.
Area of Science:
- Immunology
- Infectious Disease
- Cell Biology
Background:
- Proinflammatory CD11b+Ly6Chi monocytes were historically viewed as a uniform population.
- Recent studies suggest significant heterogeneity within this monocyte subset.
- Their roles in different infections, like Entamoeba histolytica and Listeria monocytogenes, appear context-dependent.
Purpose of the Study:
- To investigate the diversity of Ly6C high monocytes in response to distinct liver infections.
- To compare the molecular and functional profiles of these monocytes during E. histolytica and L. monocytogenes infections.
- To identify potential markers for subdividing Ly6C high monocyte populations.
Main Methods:
- Analysis of Ly6C high monocytes from mouse liver models of E. histolytica and L. monocytogenes infection.
- Transcriptomic, proteomic, and functional assays were employed.
- Comparison of monocyte populations from infected and naive mice.
Main Results:
- Both infections led to Ly6C+ monocyte accumulation, with distinct chemokine profiles.
- E. histolytica infection showed monocyte similarity to naive states, with M2-related transcription factor upregulation (Mafb, Nr4a1, Fos) and higher CD14 expression.
- L. monocytogenes infection induced a clear proinflammatory phenotype with M1-related transcription factor expression (Irf2, Mndal, Ifi204), higher CD38, CD74, CD86, and increased ROS production.
Conclusions:
- Proinflammatory Ly6C high monocytes exhibit considerable variation based on the specific pathogen.
- Distinct molecular signatures differentiate monocyte responses to E. histolytica and L. monocytogenes.
- The identified markers allow for further subdivision of Ly6C high monocyte populations, enhancing our understanding of immune responses.
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