Immunobiology of Plasmodium in liver and brain

Abstract

Malaria remains one of the most serious health problems globally, but our understanding of the biology of the parasite and the pathogenesis of severe disease is still limited. Multiple cellular effector mechanisms that mediate parasite elimination from the liver have been described, but how effector cells use classical granule-mediated cytotoxicity to attack infected hepatocytes and how cytokines and chemokines spread via the unique fluid pathways of the liver to reach the parasites over considerable distances remains unknown. Similarly, a wealth of information on cerebral malaria (CM), one of the most severe manifestations of the disease, was gained from post-mortem analyses of human brain and murine disease models, but the cellular processes that ultimately cause disease are not fully understood. Here, we discuss how imaging of the local dynamics of parasite infection and host response as well as consideration of anatomical and physiological features of liver and brain can provide a better understanding of the initial asymptomatic hepatic phase of the infection and the cascade of events leading to CM. Given the increasing drug resistance of both parasite and vector and the unavailability of a protective vaccine, the urgency to reduce the tremendous morbidity and mortality associated with severe malaria is obvious.

TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected withPlasmodium bergheiANKA

“…Evidence suggests that the innate immune response plays an important role during the early phase of infection, with activated monocytes and neutrophils releasing nonspecific inflammatory mediators such as ROS and cytokines [2, 39] and exerting their roles as phagocytes and antigen-presenting cells when in contact with circulating infected RBCs [40]. Indeed, phagocytosis of infected RBCs by peripheral blood and tissue phagocytes is suggested to be the major mechanism of Plasmodium removal [41].…”

Advances in molecular genetic systems in malaria

“…Using intravital microscopy of transgenic parasites that express bioluminescent or fluorescent proteins, it is now also possible to trace the journey of parasites in vivo in tissues such as the liver, brain and spleen, which have fundamental roles in the establishment of infection, pathogenesis and clearance of infection 19,[128][129][130] . Technological advances in microscopy, such as two-photon microscopy, are providing even greater scope for imaging living tissue at the cellular level 131,132 .…”

From within host dynamics to the epidemiology of infectious disease: Scientific overview and challenges

“…Innate immune responses are activated, which at present are largely unexplored [54]. Surviving sporozoites migrate to the liver, where they take temporary refuge in hepatocytes [55]. There, one sporozoite can multiply within a week to 10 days to form tens of thousands of distinctly different asexual parasite forms, called merozoites.…”