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IMS BHU (PhD work) ICGEB

JHMI/URMC NY BLOOD CENTER

Platelets are Immunological Cells that influence the T Cells 

Kalyan Srivastava, PhD

Falciparum malaria is a major cause of lethality

Cerebral Malaria (CM) Overview

CM is a severe complication of P. falciparum infection Endemic in sub-Saharan Africa, Indian subcontinent and South

America More than a million people die from falciparum infection each

year Majority death is among children less than five More than 20% of malaria death is due to the CM impaired consciousness, convulsions and neurological

abnormalities, ataxia and coma Diagnosis done by retinopathy Increased serum ET-1, ICAM-1, TNFalpha in pateint Platelets Play Cruicial Role in Malaria InfectionSevere malaria is

associated with thrombocytopeniaReduced platelet count often first sign before clinical symptoms

Platelets have been implicated to have central role in cerebral malaria

Other in part platelet derived molecules such as TGFbeta, PAF, P-Sel has been reported to high in malaria infection

CXCR3, CCR5 and CCR1in cerrebral malaria

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PF4 or CXCL4

PF4 are platelet specific chemokine produced from Platelet and T Cell to some extent

Implicated in HIT

First ever discovered CXC chemokine

Implicated in viral infection and stroke

Found in alpha granule of platelets

One known receptor is CXCR3

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Platelets are activated by iRBC via CD36 on platelets

• Activated platelet result into the pathogenesis of ECM

PF4 Drives the Development of ECM

PF4 Promotes Immune Stimulation and T Cell Trafficking in ECM

• Monocytes and platelets both play critical roles in atherogenesis.

• In later work have shown that PF4, activates monocytes and results in progression of diseases such as Cerebral Malaria (CM).

• PF4 mediated KLF4 expression and activation leads to the Mono/Mac activation

Summary

Platelets have machinery for antigen presentation

Platelets process the antigen to present it to T Cell

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Platelets exposed to antigen are protective in CM

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• CM is a consequence of blood brain barrier break down

• Plts play imp role • PF4 plays imp role• IFNbeta is protective in MS• Plts participate in Ag presentation• Plts participate in acute phase response• Plts participate in transplant rejection• … all of it via T Cell response.

IFNbeta suppresses ECM associated inflammation

IFNbeta reduces Tcell trafficking studied using flow

IFNbeta is protective in CM

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PF4 Stimulates KLF4 Activity

Monocytes are Important in the Development of ECM

PF4 Mediates KLF4 Expression in ECM

7/8/14IL-6 was measured by ELISA