Thus, high temperature causes an increase in the expression and chaperone activ ity of PfHsps causing increased trafficking AMN-107 of KAHRP and ETRAMP5, leading to increased PfEMP1 presentation on the pRBC membrane. Figure 2a shows PPI associated with PfEMP1 presentation and sequestration. Platelet activation Glycoprotein integrin gpIIIa is seen to interact with the merozoite surface protein MSP 1. MSP 1 is initially expressed as a protein precursor, which undergoes pri mary proteolytic processing within the pRBC during late trophozoite and schizont stages resulting in four frag ments. All the remaining fragments, except for the p19 Glycosylphosphatidylinositol anchor present on the pRBC, are shed during schizogony to form a complex in association with MSP 6 and MSP 7.

Platelets are known to be activated via membrane glycoprotein integ rins such as gpIIb IIIa. It is known that parasite derived products released at schizogony can act as trig gers for platelet activation via platelet membrane glyco proteins followed by TGF B release. It can be hypothesized that the MSP 1 complex interacts with gpIIIa in vivo resulting in platelet activation. On the other hand, platelets can also get activated on contact with pRBCs. It is possible that the MSP 1 GPI anchor on the pRBC surface interacts with gpIIIa during platelet pRBC contact resulting in platelet activation. Thus, there are two possible in vivo scenarios for the MSP 1 gpIIIa interaction to occur. A set of interactions between TGF B and parasite pro teins as well as those between TGF B receptors and para site proteins are observed.

Regulation by parasite factors is through direct interactions involving TGF B or through interactions with platelets resulting in TGF B release. Experimental evidence suggests that PfTRAP activates latent TGF B. This activation is harmful during the early stages of the infec tion since TGF B down regulates the inflammatory cytokines resulting in reduced parasite clearance. How ever, in the later stages of the disease, TGF B activation may be protective through the down regulation of the systemic inflammation. Hence, the role of TGF B could depend on the time of its activation by parasite proteins, with activation in early stages resulting in increased para site clearance time. TGF B released by activated platelets transduces signals by binding to TGF B receptor type I and TGF B receptor type II.

TGF B receptor mediated signaling is crucial in endothe lial apoptosis. It is also known that the antagonistic binding of inhibitory proteins on TGF B receptors Dacomitinib inter feres with TGF B signaling and causes changes in the nor mal functioning of TGF B. Though the exact function of the parasite proteins involved in the PPI is currently unknown, it is possible that parasite proteins might interfere in TGF B receptor mediated signaling. Figure 2b shows PPI associated with platelet activation and their probable linkage to haemostasis dysfunction systemic inflammation.