Hidden diversity: Identification and characterisation of compartment-specific testicular macrophage populations

Two major populations of resident macrophages have been identified in the mouse testis: interstitial tissue macrophages, characterised by high expression of CD206 and low or undetectable MHC class II antigen (MHCII) expression, and peritubular macrophages that generally lack CD206, but exhibit elevated MHCII. A morphometric analysis of macrophage subset marker antigens throughout the entire adult mouse testis was undertaken employing transgenic expression of the green fluorescent protein reporter at the locus of the Cx3cr1 gene (Cx3cr1^gfp/+), and immunofluorescence localisation of F4/80, MHCII (I-A/I-E) and CD206. Compared with the testicular parenchyma encompassing the seminiferous tubules, the volume density of total macrophages (F4/80⁺) was 8-9-fold higher in the interstitial and peri-epithelial regions of the rete testis. Moreover, the majority of the interstitial and peri-epithelial macrophages in the rete testis were positive for both CD206 and MHCII - these double-positive macrophages were also numerous within and beneath the testis capsule. There was a small, but significant, increase (5-10 %) in the volume density of interstitial macrophages in the rete testis of mice with a heterozygous deletion of the Inhba (activin A subunit) gene. Macrophages increased considerably in the rete testis and adjacent testicular regions during infection with uropathogenic Escherichia coli. These data identify a substantial subset of macrophages within the mouse rete testis and subcapsular region that express both CD206 and MHCII, which comprises only a minor subset in the remainder of the testis. These double-positive macrophages may play a dual role in regulating tolerance to spermatozoa and responding to ascending infections.