The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased susceptibility to systemic spread and fatal infection by different pathogens. Severe forms of visceral leishmaniasis are associated with disorganization of spleen compartments where cell interactions essential for splenic immunological function take place. White pulp atrophies, secondary lymphoid follicles and marginal zones vanish, and the boundaries separating white and red pulp blur. Leukocyte populations are reduced or disappear or are replaced by plasma cells. In this paper, we review the published data on spleen disorganization in severe forms of visceral leishmaniasis and propose a histological classification to help the exchange of information among research groups.

Universal influenza vaccines should protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines, as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell–inducing nucleoside-modified messenger RNA (mRNA) vaccine that encodes the conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly reactive T cells in the circulation, bone marrow, and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.

Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum or L. donovani infection. One of the main problems related to this disease is the emergence of severe clinical forms with a lethality of 5-20%, even while under specific treatment. In humans and other species susceptible to fatal VL, such as dogs and hamsters, the disruption of splenic white pulp (WP) is accompanied by disease progression. Control of VL progression is seen in BALB/c mice, as evidenced by a mild clinical presentation and controlled parasite replication in the liver and spleen. In this study, we investigated the features involved in the morphological remodeling of splenic compartments associated with the control of VL progression to death. Methods: We evaluated cohorts of BALB/c mice after 30, 60, and 90 days of infection by L. infantum. Spleen morphology, cell population subsets and cytokine production were studied in the spleen using flow-and histo-cytometry. Results: Intraperitoneal infection with 10 8 promastigotes of L. infantum led to progressive increases in spleen size at 60 and 90 days after infection. Splenomegaly was the only clinical sign of disease observed. At 30 days after infection, hyperplasia in the WP and decreased numbers of plasmacytoid dendritic cells were observed. The WP hyperplasia subsided at 60 days post-infection. However, the splenomegaly remained in association with increased numbers of macrophages, B and T lymphocytes and plasma cells. An increased number of lymphoid tissue inducer (LTi) cells was observed; these were distributed around the periarteriolar lymphoid sheath in control mice and scattered throughout the red pulp in the Leishmania-infected mice. After 90 days of infection, increased IL-6 and IFN-γ production was seen in the spleen, as well as higher frequencies of follicular and plasmacytoid dendritic cells. Conclusion: The data presented herein emphasizes the potential role of spleen remodeling in the control of severe forms of VL and highlights features potentially involved in this process.

The data presented herein suggest the occurrence of changes in the distribution of nephrological diseases in Salvador, Brazil. The disease that was most prevalent shifted from membranoproliferative glomerulonephritis to focal and segmental glomerulosclerosis from 1975 to 2006 and from focal and segmental glomerulosclerosis to lupus nephritis from 2006 to 2015.

Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased DLK1 expression. The expression of CXCL13, CCR5, CCL19, CCR6, CCR7 and LTA decreased, likely regulated by CDKN2A overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.