10.1371/journal.pone.0130092 Kristin L. Rosche Kristin L. Rosche Alanoud T. Aljasham Alanoud T. Aljasham James N. Kipfer James N. Kipfer Bryan T. Piatkowski Bryan T. Piatkowski Vjollca Konjufca Vjollca Konjufca Infection with <i>Salmonella enterica</i> Serovar Typhimurium Leads to Increased Proportions of F4/80<sup>+</sup> Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen Public Library of Science 2015 Salmonella infection rp cell distributions RBC precursors lymphocytes lymphocyte proportions macrophages decrease wp spleen microarchitecture impact ifm flow cytometry Spleen Infection Decreased Proportions Salmonella enterica Serovar Typhimurium understanding Salmonella pathogenesis MZ MOMA Blood cells T lymphocytes splenic tissue architecture splenomegaly color immunofluorescence microscopy Spleen tissue sections show cell population proportions tissue architecture recycling senescent spleen tissue 2015-06-12 03:53:47 Dataset https://plos.figshare.com/articles/dataset/Infection_with_Salmonella_enterica_Serovar_Typhimurium_Leads_to_Increased_Proportions_of_F4_80_Red_Pulp_Macrophages_and_Decreased_Proportions_of_B_and_T_Lymphocytes_in_the_Spleen/1448168 <div><p>Infection of mice with <i>Salmonella enterica</i> serovar Typhimurium (<i>Salmonella</i>) causes systemic inflammatory disease and enlargement of the spleen (splenomegaly). Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71<sup>+</sup>Ter119<sup>+</sup> reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs) and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP), marginal zone (MZ), and red pulp (RP) is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM), we show that <i>Salmonella</i>-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80<sup>+</sup> macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220<sup>+</sup>, CD4<sup>+</sup> and CD8<sup>+</sup> lymphocytes, as well as MZ MOMA<sup>+</sup> macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80<sup>+</sup> macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80<sup>+</sup> macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during <i>Salmonella</i> infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to <i>Salmonella</i> has implications for understanding <i>Salmonella</i> pathogenesis and for the design of more effective <i>Salmonella</i>-based vaccines.</p></div>