The role of the gp85/trans-sialidases in T. cruzi
infection has been extensively demonstrated by several groups, including ours, although the exact mechanism by which the members of this large gene family mediate parasite cell invasion is still unclear. Different molecules have been identified as putative ligands for gp85/trans-sialidase family members and the pan-specificity toward so many distinct proteins has been explained by the existence of hundreds of gp85/transialidases sharing variable degrees of similarity: different proteins, different ligands. This hypothesis is corroborated by findings, for example, from our group that only a sub-set of acidic gp85/trans-sialidase glycoproteins binds to laminin-1 
. However, in contrast with this line of thought, a highly conserved peptide sequence present in all gp85/trans-sialidase family members promotes organ-selective endothelial cell binding, possibly, by interacting with different intermediate filament proteins, in particular, those belonging to the cytokeratin family or to vimentin.
Intermediate filaments are important components of the cytoskeleton, present in nearly every eukaryotic cell 
. They are comprised of proteins structurally related, including cytokeratins, vimentin and nuclear lamins. The binding of the FLY peptide to different cytokeratins is not unexpected given the high similarity among family members. But the interaction of FLY peptide with vimentin is an interesting finding and suggests that FLY might bind to intermediate filament proteins in general. And since intermediate filament proteins share a common structure and cellular functions 
but their expression pattern vary, it is possible that T. cruzi
selected a common binding site shared by different intermediate filament proteins in order to invade a wider variety of cells and tissues. Our data is in agreement with this hypothesis as suggested by the interaction of FLY peptide with CK8 (expressed by muscle cells, epithelial cells), CK20 (epithelial cells) and vimentin (endothelial cells). However, we cannot rule out the participation of other intermediate filament proteins as putative receptors for the parasite because many of these structural proteins have overlapping expression patterns and are often expressed by different cells in multiple tissues. For example, cytokeratin intermediate filaments are heteropolymers formed from equal amounts of type I and type II keratin chains. In fact, the heterodimeric nature of cytokeratin filaments may also explain why parasites still enter cells in which only CK18 expression has been reduced by transient RNA interference 
Other studies have already pointed to the presence and importance of cytokeratins in non-epithelial tissues, and more specifically, the heart. Cardiac myocytes express CK8, CK18 and CK19 
, including the myocardial endothelium compartment 
; absence of CK19 results in loss of contractile force and myopathy 
. CK18 and a fragment of CK18 (produced by caspase cleavage) have also been reported as markers for myocardial damage 
. Interestingly, the caspase cleaved-CK18 fragment seems to accumulate in myocardial lysosomes 
and because these organelles have a prominent role in parasite cell entering 
, it is tempting to speculate that there might exist a correlation between these two phenomena. In summary, our data point to an important role of intermediate filament proteins in T. cruzi
cell entering and infection. These proteins, however, are ubiquitously expressed by virtually all eukaryotic cells and new approaches ought to be considered in order to fully appreciate their individual contribution to Chagas' disease.
Finally, using phage as a surrogate and a well established in vivo
homing assay, we show that the FLY peptide mediates phage distribution to different organs of the mouse with remarkable parallel to the tissue tropism observed in human disease and animal models 
. Worth mentioning is the strong binding of FLY phage to the heart vasculature, one of the most affected organs in patients with symptoms of chronic Chagas' disease. Almost 70% of the patients show some form of heart dysfunction and die of cardiac problems 
. These results indicate that the FLY peptide might be an important contributor to tissue tropism, delivering a higher load of parasite to these tissues. It also supports the notion that the vasculature and the endothelial cells are important players in Chagas' disease. Taken together, our data on endothelial cell immortalization and phage display unveiled the important contribution of two large families of proteins, the intermediate filament proteins and the gp85/transialidases, in T. cruzi
tissue tropism. These data may have important implications in the pathology of Chagas' disease and novel therapeutic approaches for patients afflicted with this disease.