Invited ReviewThe role of TNF in parasitic diseases: Still more questions than answers
Graphical abstract
Section snippets
TNF and its two receptors
TNF was first named in 1975 as an endotoxin-induced factor that effected the necrosis of established tumors (Carswell et al., 1975). The biology of TNF was further characterised over the next 10 years in two parallel lines of research that studied two fundamentally different metabolic activities of this cytokine: its ability to induce cell death in certain transformed cell lines (Old, 1985, Espevik and Nissen-Meyer, 1986) and its suppression of the enzyme lipoprotein lipase A (Kawakami et al.,
TNF and its receptors in malaria
Symptomatic malaria infection arises when the causative parasite, Plasmodium spp., invades and replicates within circulating erythrocytes, frequently causing relatively mild symptoms such as nausea and fever, but occasionally more severe problems such as anaemia, respiratory distress and cerebral malaria (CM). In CM Plasmodium falciparum-infected erythrocytes cyto-adhere to the brain microvasculature, resulting in a massive functional disturbance of the brain that is often life threatening.
Concluding remarks
The role of TNF has been investigated in many experimental models of infection. The results which have been reported are not always consistent and sometimes surprisingly contradictory. This review highlights that the genomic make-up of knockout models used to study TNF or TNFR could be a contributing factor to the different outcomes in experimental models of intracellular infection, keeping in mind that back-crossing five generations leaves approximately 3% of non-linked genes from the founder
Acknowledgements
The authors wish to acknowledge the financial support of the NHMRC, the DFG (Schl 392/6-1 to DS) and the Medical Genetics Research Advancement Program (JCU to HK).
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