The schistosomiasis spleenOME : unveiling the proteomic landscape of splenomegaly using label-free mass spectrometry.
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Date
2019
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Abstract
Schistosomiasis is a neglected parasitic disease that affects millions of people worldwide
and is caused by helminth parasites from the genus Schistosoma. When caused by S.
mansoni, it is associated with the development of a hepatosplenic disease caused by
an intense immune response to the important antigenic contribution of adult worms
and to the presence of eggs trapped in liver tissue. Although the importance of the
spleen for the establishment of immune pathology is widely accepted, it has received little
attention in terms of the molecular mechanisms operating in response to the infection.
Here, we interrogated the spleen proteome using a label-free shotgun approach for
the potential discovery of molecular mechanisms associated to the peak of the acute
phase of inflammation and the development of splenomegaly in the murine model. Over
fifteen hundred proteins were identified in both infected and control individuals and
325 of those proteins were differentially expressed. Two hundred and forty-two proteins
were found upregulated in infected individuals while 83 were downregulated. Functional
enrichment analyses for differentially expressed proteins showed that most of them were
categorized within pathways of innate and adaptive immunity, DNA replication, vesicle
transport and catabolic metabolism. There was an important contribution of granulocyte
proteins and antigen processing and presentation pathways were augmented, with the
increased expression of MHC class II molecules but the negative regulation of cysteine
and serine proteases. Several proteins related to RNA processing were upregulated,
including splicing factors. We also found indications of metabolic reprogramming in
spleen cells with downregulation of proteins related to mitochondrial metabolism. Ex-vivo
imunophenotyping of spleen cells allowed us to attribute the higher abundance of MHC
II detected by mass spectrometry to increased number of macrophages (F4/80+/MHC
II+ cells) in the infected condition. We believe these findings add novel insights for
the understanding of the immune mechanisms associated with the establishment of
schistosomiasis and the processes of immune modulation implied in the host-parasite
interactions.
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Keywords
Schistosoma manson, Host-parasite interactions, Proteome, Helminthiasis, Acute inflammation
Citation
COSENZA CONTRERAS, M. de J. et al. The schistosomiasis spleenOME : unveiling the proteomic landscape of splenomegaly using label-free mass spectrometry. Frontiers in Immunology, v. 9, p. 1-17, jan. 2019. Disponível em: <https://www.frontiersin.org/articles/10.3389/fimmu.2018.03137/full>. Acesso em: 21 fev. 2019.