Tissue resident macrophages have vital homeostatic roles, often acting as professional scavengers, phagocytosing apoptotic cells and debris. Well characterised resident populations exist in liver, brain, as well as peritoneal cavity but are less well defined in the heart.
Histological analysis of naive hearts from CSF1 receptor (MacGreen) and CX3CR1 GFP reporter mice revealed a sparse population of GFP +ve cells (8.6 ± 0.7 GFP+ cells per field (cpf) x 40 mag). This was supported by flow cytometric evaluation of digested hearts from which <25,000 F4/80+CD11b+ macrophages (100–130 per mg tissue) were recoverable. In comparison with peritoneal macrophages, as a typical resident macrophage population, cardiac macrophages had lower expression of CD64 (50% vs 90%, p < 0.01). Cardiac macrophages also had a lower % of MHC Class II high cells than peritoneal macrophages (p < 0.05), as well as lower F4/80 (p < 0.05) and CD11b+ expression (p < 0.0001). These differences may reflect the different functions, maturity and/or origins of these two populations. FACS sorted cardiac macrophages expressed markers typical of both ‘M1’ (iNOS, TNF and CCR2) and ‘M2’ activation (Ym1, Arg 1, RELMa and IL-10), suggesting no specific polarisation in healthy myocardium. In a functional assay cardiac macrophages were more phagocytically active than peritoneal macrophages (2.85 ± 0.25 vs 1.03 ± 0.03% +ve for ingested fluorospheres p < 0.01), and also expressed more of phagocytosis associated TREM2 (1.09 ± 0.04 vs 0.7 ± 0.04 AU, p < 0.01).
Following infection with the parasite Schistosoma mansoni, CX3CR1gfp/+ mice had a significantly higher density of immunopositive cells (43.4 gfp+ cpf, P < 0.01), with increased representation of cells that were “stellate” in shape with elongated/dendritic projections (10 ± 0.7 vs 1 ± 0.1 cpf, p < 0.01). In addition, only hearts from S. mansoni infected mice contained ‘M2’-like RELMalpha +ve cells and expression of the ‘M2’ marker, Ym1, was also significantly increased (p < 0.01), consistent with polarisation induced by infection.
In conclusion, we describe a sparse resident murine cardiac macrophage population that is not overtly polarised but has phagocytic capability. These macrophages increase in number, change shape and become ‘M2’ polarised in response to the ‘Th2 type’ challenge induced by parasite infection. These observations may have implications for regulation of the myocardial response to injury during helminth infection and in other instances of Th2 dominated inflammation.
Sponsored by the Wellcome Trust (PG-WT091720) and by British Heart Foundation Centre of Research Excellence Award.
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