This document discusses cerebral malaria (CM), a severe complication of Plasmodium falciparum infection that is a major cause of death in children under 5 years old in parts of Africa and Asia. It notes that platelets play a crucial role in malaria infection, with reduced platelet count often preceding clinical symptoms. Specifically, it discusses how the platelet-derived chemokine PF4 drives the development of CM by promoting immune stimulation and T cell trafficking. It also describes how PF4 mediates KLF4 expression and activation in monocytes, leading to their activation and contributing to the progression of diseases like CM.

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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

2. Falciparum malaria is a
major cause of lethality

3. 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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6. Platelets are activated by iRBC via CD36 on platelets

7. • Activated platelet result into the pathogenesis of ECM

8. PF4 Drives the
Development of ECM

9. PF4 Promotes
Immune
Stimulation and T
Cell Trafficking in
ECM

10. • 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

11. Summary

13. Platelets have machinery for
antigen presentation

14. Platelets process the antigen to present it to T Cell

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16. Platelets exposed to antigen
are protective in CM

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24. • 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.

25. IFNbeta suppresses ECM
associated inflammation

26. IFNbeta reduces Tcell
trafficking studied using
flow

27. IFNbeta is protective in CM

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30. PF4 Stimulates KLF4 Activity

31. Monocytes are Important in the
Development of ECM

32. PF4 Mediates KLF4 Expression in ECM

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IL-6 was measured by ELISA