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

PLoS Negl Trop Dis. 2024 Jun 6;18(6):e0011877. doi: 10.1371/journal.pntd.0011877. eCollection 2024 Jun.

Abstract

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.

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • Coinfection* / virology
  • Female
  • Gene Expression
  • HIV Infections* / complications
  • Humans
  • Leishmania infantum / genetics
  • Leishmaniasis, Visceral* / genetics
  • Leishmaniasis, Visceral* / parasitology
  • Male
  • Spleen* / pathology

Grants and funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (Financial support grant no. 424776/2016-2 to WLCS; Research productivity scholarship to WLCS; Scholarship "Bolsa Jovem Talentos" to RK) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES (Financial support to WLCS; PhD scholarship to JLFM; PhD scholarship to CVBM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.