PLoS Neglected Tropical Diseases (Jun 2024)

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

  • Jonathan L M Fontes,
  • Ricardo Khouri,
  • Luis Gustavo C Reinaldo,
  • Erina M A Hassegawa,
  • Antônio José Meneses Filho,
  • Caroline V B de Melo,
  • Pablo Ivan P Ramos,
  • Rafael de Deus Moura,
  • Carla Pagliari,
  • Marta Santos,
  • Raimundo José C Araújo,
  • Johan Van Weyenbergh,
  • Luiz A R de Freitas,
  • Carlos Henrique N Costa,
  • Washington L C Dos-Santos

DOI
https://doi.org/10.1371/journal.pntd.0011877
Journal volume & issue
Vol. 18, no. 6
p. e0011877

Abstract

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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.