Spatial transcriptomics of an innate granuloma in a mouse infection model with Chromobacterium violaceum

From Amason et al., 2024. "Granulomas are defined by the presence of
organized layers of immune cells that include macrophages. Granulomas are
often characterized as a way for the immune system to contain an infection
and prevent its dissemination. We recently established a mouse infection
model where Chromobacterium violaceum induces the innate immune system to
form granulomas in the liver. This response successfully eradicates the
bacteria and returns the liver to homeostasis. Here, we sought to
characterize the chemokines involved in directing immune cells to form the
distinct layers of a granuloma. We use spatial transcriptomics to
investigate the spatial and temporal expression of all CC and CXC
chemokines and their receptors within this granuloma response. The
expression profiles change dynamically over space and time as the
granuloma matures and then resolves. To investigate the importance of
monocyte-derived macrophages in this immune response, we studied the role
of CCR2 during C. violaceum infection. Ccr2–/– mice had negligible numbers
of macrophages, but large numbers of neutrophils, in the C.
violaceum-infected lesions. In addition, lesions had abnormal architecture
resulting in loss of bacterial containment. Without CCR2, bacteria
disseminated and the mice succumbed to the infection. This indicates that
macrophages are critical to form a successful innate granuloma in response
to C. violaceum."