The Properties of Proinflammatory Ly6C hi Monocytes Are Differentially Shaped by Parasitic and Bacterial Liver Infections.

In the past, proinflammatory CD11b + Ly6C hi 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 Ly6C hi 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 Ly6C hi 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 Ly6C hi monocytes vary considerably depending on the causative pathogen. By using markers identified in the study, Ly6C hi monocytes can be further subdivided into different populations.