Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection

JUIZ, NA; SOLANA ME; ACEVEDO, GR; BENATAR AF; RAMIREZ JC; ALMEIDA DA COSTA P; MACEDO AM; LONGHI SA; SCHIJMAN, AG

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2017

1935-2735

Congenital infection of Trypanosoma cruzi allows transmission of this parasite through generations.Despite the problematic that this entails, little is known about the placenta environmentgenetic response produced against infection. We performed functional genomics bymicroarray analysis in C57Bl/6J mice comparing placentas from uninfected animals andfrom animals infected with two different T. cruzi strains: K98, a clone of the non-lethal myotropicCA-I strain (TcI), and VD (TcVI), isolated from a human case of congenital infection.Analysis of networks by GeneMANIA of differentially expressed genes showed that ªSecretoryGranuleº was a pathway down-regulated in both infected groups, whereas ªInnateImmune Responseº and ªResponse to Interferon-gammaº were pathways up-regulated inVD infection but not in K98. Applying another approach, the GSEA algorithm that detectssmall changes in predetermined gene sets, we found that metabolic processes, transcriptionand macromolecular transport were down-regulated in infected placentas environment andsome pathways related to cascade signaling had opposite regulation: over-represented inVD and down-regulated in K98 group. We also have found a stronger tropism to the placentalorgan by VD strain, by detection of parasite DNA and RNA, suggesting living parasites.Our study is the first one to describe in a murine model the genetic response of placentalenvironment to T. cruzi infection and suggests the development of a strong immuneresponse, parasite genotype-dependent, to the detriment of cellular metabolism, which maycontribute to control infection preventing the risk of congenital transmission.PLOS Neglected