An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection.

The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen. Author summary: While most individuals recover after contracting visceral leishmaniasis, there are cases where patients experience a relapsing form of the disease. This response pattern to Leishmania infection is linked to alterations in spleen structure. Until now, these spleen changes had only been examined in dogs and laboratory animals. In our study, we provide data on the disorganization of spleen structure in three patients diagnosed with VL, two of whom were also co-infected with HIV. The observed patterns of spleen disorganization closely resembled those seen in dogs. Our study emphasizes the involvement of IL6, BCL10, and ICOSLG in this process. [ABSTRACT FROM AUTHOR]