<i>S.</i> Typhimurium-infected mice have tissue inflammation and thrombosis, increased hematopoiesis, and decreased splenic iron.

<p>(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 TER119^med pro-erythroblasts and 5.5-fold more TER119^high erythroblasts than the mock-infected mouse. (G) Mean numbers of TER119^med and TER119^high splenocytes from three mock-infected (white bars) and four infected (gray bars) mice. Mean number of TER119^med pro-erythroblasts per spleen increased 6.8-fold in infected mice, while the mean number of TER119^high cells, corresponding to all nucleated erythroblasts subsequent to the pro-erythroblast stage <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009441#pone.0009441-Socolovsky1" target="_blank">[40]</a>, increased 3.6-fold. (<i>P</i><0.05) Error bars = SD. Original magnifications 100× (A–B), 200× (C–D), and 1000× (E).</p

Hematology of <i>S.</i> Typhimurium-infected mice: acute, then chronic active inflammatory response; microcytic anemia, persistent microcytosis.

<p>Mice were orally gavaged with 9.1×10⁸ CFU of <i>S</i>. Typhimurium (n = 8) or sterile PBS (n = 7). Complete blood counts were monitored over 16 weeks. X  =  <i>S</i>. 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). *<i>P</i><0.05 (Student's <i>t</i>-test).</p

Clinico-pathologic features of HLH in <i>S.</i> Typhimurium-infected mice.

<p>PI indicates post-oral infection with 2.0×10⁹ CFU <i>Salmonella enterica</i> serotype Typhimurium; C indicates mock-infected control mice.</p>*<p><i>P</i><0.05, Student's <i>t</i>-Test.</p>†<p>Independent experiment, same bacterial dosing and range for splenic bacterial CFU results.</p>‡<p>Formal diagnostic criteria for HLH per the Histiocyte Society guidelines <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009441#pone.0009441-Henter1" target="_blank">[5]</a>.</p>§<p>Consistent with a diagnosis of HLH, and ^Π strong supportive evidence for HLH <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009441#pone.0009441-Henter1" target="_blank">[5]</a>.</p