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.

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The extent to which hybridization disrupts a gene’s pattern of expression likely governs its propensity for introgression, while its extent of molecular divergence can itself underlie such disruption. Together, these phenomena shape the landscape of sequence and transcriptional divergence across the genome as species diverge. To understand this process, we examine gene expression inheritance, regulatory and molecular divergences in the reproductive transcriptomes of species linked by gene flow. The fruit flies Anastrepha fraterculus and A. obliqua show evidence of gene flow despite clear evolutionary divergence and incomplete reproductive isolation. We find that their transcriptional patterns are a mosaic between those typically observed within and between allopatric species. Genes showing transgressive expression in hybrids or cis-regulatory divergence between species are associated with greater molecular divergence. This may reflect pleiotropic constraints that make them more resistant to gene flow or they may be more likely to experience divergent selection. However, while these highly divergent genes are likely to be important contributors to species differences, they are relatively rare. Instead, most differentially regulated genes, including those linked to reproduction, show high degrees of dominance in hybrids and trans-regulated divergence between species, suggesting widespread genetic compatibility that allowed for the identified introgression. These findings provide insights into how postzygotic isolating mechanisms might evolve in the presence of gene flow: regions showing cis-regulatory divergence or transgressive expression contribute to reproductive isolation, while regions with dominant expression and trans-regulatory divergence act as a buffer of hybrid breakdown, facilitating introgression, and leading to a genomic mosaic of expression and sequence divergence.

The spleen is involved in visceral leishmaniasis immunopathogenesis, and presents alterations in white-pulp microenvironments that are associated with an increased susceptibility to coinfections and patient death. Plasmacytosis in splenic red pulp (RP) is one observed alteration, but the specificity of antibody-secreting cells and the distribution of them has not yet been evaluated. We biotinylated soluble L. infantum membrane antigens (bSLMA) used as probes in modified immunohistochemistry, and detected the presence of anti-L. infantum antibody-secreting cells. Were used spleens from eight dogs from the endemic area for canine visceral leishmaniasis (CanL), and three healthier controls. The spleen sections were cryopreserved, and we performed modified immunohistochemistry. The ratio of plasma cells which were reactive to bSLMA (Anti-Leish-PC) in the spleen RP and periarteriolar lymphatic sheath (PALS) were calculated. Dogs with CanL present hyperglobulinemia and more plasma cells in their RP than the controls. Furthermore, dogs with CanL presented a lower proportion of Anti-Leish-PC in their RP than in PALS. Likewise, dysproteinemia was related to RP and PALS plasmacytosis, and a more severe clinical profile.