Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection.
It is thought that Trypanosoma cruzi, the protozoan that causes Chagas' disease, modulates the extracellular matrix network to facilitate infection of human cells. However, direct evidence to document this phenomenon is lacking. Here we show that the T. cruzi gp83 ligand, a cell surface trans-sialidase-like molecule that the parasite uses to attach to host cells, increases the level of laminin gamma-1 transcript and its expression in mammalian cells, leading to an increase in cellular infection. Stable RNA interference (RNAi) with host cell laminin gamma-1 knocks down the levels of laminin gamma-1 transcript and protein expression in mammalian cells, causing a dramatic reduction in cellular infection by T. cruzi. Thus, host laminin gamma-1, which is regulated by the parasite, plays a crucial role in the early process of infection. This is the first report showing that knocking down the expression of a human gene by RNAi inhibits the infection of an intracellular parasite.
Nde
Pius N
PN
Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, School of Medicine, Meharry Medical College, 1005 Dr. D. B. Todd Jr. Blvd., Nashville, TN 37208, USA.
Simmons
Kaneatra J
KJ
Kleshchenko
Yuliya Y
YY
Pratap
Siddharth
S
Lima
Maria F
MF
Villalta
Fernando
F
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D014355:Chagas Disease / Q000517:prevention & control; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D007797:Laminin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics
D000953:Antigens, Protozoan; D007797:Laminin; D015800:Protozoan Proteins; D034741:RNA, Small Interfering; C089141:laminin gamma 1; D009439:Neuraminidase