Gene network analysis during early infection of human coronary artery smooth muscle cells by Trypanosoma cruzi and Its gp83 ligand.
Trypanosoma cruzi, the causative agent of Chagas' disease, infects heart and muscle cells leading to cardiac arrest, followed by death. The genetic architectures in the early T. cruzi infection process of human cells are unknown. To understand the genetic architectures of the early invasion process of T. cruzi, we conducted gene transcription microarray analysis, followed by gene network construction of the host cell response in primary human coronary artery smooth muscle (HCASM) cells infected with T. cruzi or exposed to T. cruzi gp83, a ligand used by the trypanosome to bind host cells. Using seven RT-PCR verified up-regulated genes (FOSB, ATF5, INPP1, CCND2, THBS1, LAMC1, and APLP2) as the seed for network construction, we built an interaction network of the early T. cruzi infection process containing 165 genes, connected by 598 biological interactions. This interactome network is centered on the BCL6 gene as a hub. Silencing the expression of two seed genes (THBS1 and LAMC1) by RNAi reduced T. cruzi infection. Overall, our results elucidate the significant and complex process involved in T. cruzi infection of HCASM cells at the transcriptome level. This is the first elucidation into the interactome network in human cells caused by T. cruzi and its gp83 ligand.
Nde
Pius N
PN
Department of Microbiology and Immunology, School of Medicine, Meharry Medical College, 1005 Dr. D. B. Todd Jr. Blvd., Nashville, TN 37208-3599, USA.
Johnson
Candice A
CA
Pratap
Siddharth
S
Cardenas
Tatiana C
TC
Kleshchenko
Yuliya Y
YY
Furtak
Vyacheslav A
VA
Simmons
Kaneatra J
KJ
Lima
Maria F
MF
Villalta
Fernando
F
D003331:Coronary Vessels / Q000166:cytology / Q000469:parasitology*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008024:Ligands; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000469:parasitology*; D020411:Oligonucleotide Array Sequence Analysis; D015800:Protozoan Proteins / Q000378:metabolism*; D034622:RNA Interference; D014158:Transcription, Genetic; D014349:Trypanosoma cruzi / Q000502:physiology*; D015854:Up-Regulation
D008024:Ligands; D015800:Protozoan Proteins