Fig 2: Quantification of innate cellular immune responses in canine distemper virus (CDV)-infected lungs. MHC-II (A–C), Iba-1 (D–F) and CD204 (G–I) antigen detection. Groups: 1 = non-infected control lungs; 2 = acute CDV infection; 3 = subacute CDV infection; 4 = subacute-chronic CDV infection; box and whisker plots display median and quartiles with maximum and minimum values. Significant differences (p = 0.05, Kruskal–Wallis H test) are labelled by asterisks.

Fig 3: MSR1 ubiquitylation and JNK activation correlate in human tumour-associated macrophages Immunohistochemistry analysis of MSR1 in patient ovarian, uterus and sarcoma cancers showing tumour-associated macrophages.Pull-downs of K63-polyubiquitin chains and IB analysis of five human primary cancers show a correlation between the amount of polyubiquitylated MSR1 and JNK activation in an ovarian tumour.Working model: MSR1 is activated by ligation through many different substrates, including apoptotic cells, fucoidan or oxidized LDL (Signal 1). However, only when the macrophage is IL-4-activated (Signal 2) becomes MSR1 ubiquitylated by an unknown E2/E3 ligase. This ubiquitylation recruits Tab2/3, Tak1, Mkk7 and finally JNK, thereby allowing MSR1 to signal directly through the JNK signalling pathway which induces pro-inflammatory gene transcription.

Fig 4: Macroscopic and histopathological findings of a 1.25 year old Chihuahua (case 1). (A) Macroscopic image of the brain with mild narrowing of sulci and flattening of gyri interpreted as edema. (B) Histopathology of the cerebral cortex at the level of the temporal lobe with moderate, leukocytoclastic vasculitis of the leptomeningeal blood vessels with fragments of degenerated inflammatory cells (arrow in insert) visible within the destructed vascular wall (HE stain; scale bar: 50µm). (C–E) Immunohistochemistry for CD3 (C), CD20 (D) and CD204 (E) shows that the majority of infiltrating cells are comprised of T-lymphocytes [(C); CD3-positive] and macrophages [(E); CD204-positive] (Scale bars: 50 µm).

Fig 5: 3D-reconstructed confocal laser images of double labelling of formalin-fixed paraffin-embedded canine spinal ganglia: Double labelling with the macrophage markers CD204 (magenta; A) and Iba1 (magenta; B) and the satellite glial cell (SGC)-specific marker glutamine synthetase (GS; green). Nuclei are counterstained with bisbenzimide (blue). Cells immunopositive for CD204 and Iba1 are in very close vicinity to GS-positive SGCs. However, there is no colocalization of GS and CD204/Iba1 detectable in SGCs. Therefore, detected cells presumably represent tissue resident macrophages. For GS/CD204 co-labelling (A), 39 z-stack frames (6.38 µm total size; approx. 0.16 µm steps) and for GS/Iba1 co-labelling (B), 34 z-stack frames (5.54 µm total size; approx. 0.16 µm steps) were acquired. Scale bars: 20 µm. A movie of 3D confocal reconstructions is provided in Video [Link], [Link] and Video [Link], [Link]