TNF family members and malaria: old observations, new insights and future directions.
Tumor necrosis factor (TNF) has long been recognized to promote malaria parasite killing, but also to contribute to the development of severe malaria disease. The precise molecular mechanisms that influence these different outcomes in malaria patients are not well understood, but the virulence and drug-resistance phenotype of malaria parasites and the genetic background and age of patients are likely to be important determinants. In the past few years, important roles for other TNF family members in host immune responses to malaria parasites and the induction of disease pathology have been discovered. In this review, we will summarize these more recent findings and highlight major gaps in our current knowledge. We will also discuss future research strategies that may allow us to better understand the sometimes subtle and intricate effects of TNF family molecules during malaria infection.
Randall
Louise M
LM
Immunology and Infection Laboratory, Queensland Institute of Medical Research and The Australian Centre for Vaccine Development, 300 Herston Road, Herston, Brisbane, Queensland, Qld 4006, Australia.
Engwerda
Christian R
CR
D000818:Animals; D005075:Biological Evolution; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000502:physiology; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D016779:Malaria, Cerebral / Q000209:etiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000502:physiology; D012641:Selection, Genetic; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000502:physiology*
D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D048069:Tumor Necrosis Factors