Table 1.
Clinico-pathologic features of HLH in S. Typhimurium-infected mice.
Figure 1.
Hematology of S. Typhimurium-infected mice: acute, then chronic active inflammatory response; microcytic anemia, persistent microcytosis.
Mice were orally gavaged with 9.1×108 CFU of S. Typhimurium (n = 8) or sterile PBS (n = 7). Complete blood counts were monitored over 16 weeks. X = S. Typhimurium-infected mice; circle = mock-infected control mice. Mean and standard deviation are shown. (A) neutrophils, (B) monocytes, (C) lymphocytes, (D) hematocrit (HCT), (E) mean cell volume (MCV). *P<0.05 (Student's t-test).
Table 2.
Hematologic parameters of S. Typhimurium-infected mice.
Figure 2.
S. Typhimurium-infected mice have increased hemophagocytic macrophages, myeloid hyperplasia, regenerative microcytic anemia and erythrocyte fragmentation.
(A) Control bone marrow cytology, 3 weeks post mock-infection. (B) Infected mouse bone marrow cytology, 3 weeks post-infection; myeloid hyperplasia with increased blasts and monocytes, hemophagocytic macrophage (white arrow), and foamy macrophage (black arrow). (C) Bone marrow histology, 6 weeks post-infection; hypercellularity with myeloid hyperplasia. (D) Mouse bone marrow cytology, 3 weeks post-infection; erythrocyte (arrow and inset) within hemophagocytic macrophage. (E) Control mouse blood film, 3 weeks post mock-infection. (F) Blood film from highly infected mouse, 3 weeks post-infection; marked erythrocyte anisocytosis, increased polychromasia and markedly fragmented erythrocytes (mature and polychromatophilic). Polychromatophilic erythrocytes (arrow-heads), fragmented polychromatophilic erythrocytes (carats), fragmented erythrocytes (arrows), L = small lymphocyte. Wright stain (A, B, D, E, F). H & E stain (C). Original magnifications 500× (A–B, D), 200× (C), or 1000× (E–F).
Figure 3.
S. Typhimurium-infected mice have tissue inflammation and thrombosis, increased hematopoiesis, and decreased splenic iron.
(A) Mouse liver, 6 weeks post-infection; inflammation and necrosis (arrow). (B) Mouse spleen, 3 weeks post-infection; extramedullary hematopoiesis (EMH; arrow, megakaryocytes), histiocytic infiltration (I) throughout the red pulp, and thrombus (T). H&E stain (A, B). (C) Spleen, mock-infected (left) and infected mouse (right), 3 weeks post-infection; markedly decreased ferric iron staining in red pulp. (D) Spleen, mock-infected (left) and infected mouse (right), 6 weeks post-infection; markedly decreased splenic ferric iron in red pulp. Perl's Prussian Blue stain (C, D). (E) Hemophagocytic macrophage in mouse spleen 3 weeks post-infection that had 10-fold more macrophages and 43-fold more 6N+ macrophages than control mouse spleen. CD11b (red), DAPI (blue), TER119 (green). N = endogenous macrophage nucleus, E1 = nucleated erythrocyte, E2 = non-nucleated erythrocyte. Confocal fluorescent micrograph. (F) Representative histogram overlay of TER119 expression on DAPI+ splenocytes from a mock-infected (red) and infected mouse (blue) 3 weeks post-infection. Filled gray histogram corresponds to the isotype control. The infected mouse had 11.5-fold more TER119med pro-erythroblasts and 5.5-fold more TER119high erythroblasts than the mock-infected mouse. (G) Mean numbers of TER119med and TER119high splenocytes from three mock-infected (white bars) and four infected (gray bars) mice. Mean number of TER119med pro-erythroblasts per spleen increased 6.8-fold in infected mice, while the mean number of TER119high cells, corresponding to all nucleated erythroblasts subsequent to the pro-erythroblast stage [40], increased 3.6-fold. (P<0.05) Error bars = SD. Original magnifications 100× (A–B), 200× (C–D), and 1000× (E).