1921
Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

malaria is one of the leading causes of childhood morbidity and mortality in sub-Saharan Africa. The host immune response to is a critical determinant of malarial pathogenesis and disease outcomes. Macrophage migration inhibitory factor (MIF) is a central regulator of innate immune responses to bacterial and parasitic infections. Our recent investigations demonstrated that peripheral blood MIF production was suppressed in children with severe malaria. Because examination of MIF production in children with active disease does not account for the inherent ability of the host to generate MIF, basal circulating MIF and peripheral blood mononuclear cell (PBMC) MIF transcript levels were determined in healthy children with a history of either mild or severe malaria. Children with prior mild malaria had higher plasma MIF levels and PBMC MIF transcripts than children with an identical number of previous episodes of severe malaria. These results suggest that increased basal MIF production may be important in generating immune responses that protect against the development of severe malaria.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2007.76.1033
2007-06-01
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/14761645/76/6/0761033.html?itemId=/content/journals/10.4269/ajtmh.2007.76.1033&mimeType=html&fmt=ahah

References

  1. Guilbert JJ, 2003. The world health report 2002—reducing risks, promoting healthy life. Educ Health (Abingdon) 16 : 230. [Google Scholar]
  2. World Health Organization, 2000. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg 94 (Suppl 1) : S1–90. [Google Scholar]
  3. Taylor T, Olola C, Valim C, Agbenyega T, Kremsner P, Krishna S, Kwiatkowski D, Newton C, Missinou M, Pinder M, Wypij D, 2006. Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network. Trans R Soc Trop Med Hyg 100 : 615–622. [Google Scholar]
  4. Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, Newbold C, Gupta S, Marsh K, 1997. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet 349 : 1650–1654. [Google Scholar]
  5. Kwiatkowski DP, 2005. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77 : 171–192. [Google Scholar]
  6. Clark IA, Alleva LM, Mills AC, Cowden WB, 2004. Pathogenesis of malaria and clinically similar conditions. Clin Microbiol Rev 17 : 509–539. [Google Scholar]
  7. Clark IA, Cowden WB, 2003. The pathophysiology of falciparum malaria. Pharmacol Ther 99 : 221–260. [Google Scholar]
  8. Awandare GA, Hittner JB, Kremsner PG, Ochiel DO, Keller CC, Weinberg JB, Clark IA, Perkins DJ, 2006. Decreased circulating macrophage migration inhibitory factor (MIF) protein and blood mononuclear cell MIF transcripts in children with Plasmodium falciparum malaria. Clin Immunol 119 : 219–225. [Google Scholar]
  9. Awandare GA, Ouma C, Keller CC, Were T, Otieno R, Ouma Y, Davenport GC, Hittner JB, Ong’echa JM, Ferrell R, Perkins DJ, 2006. A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria. Genes Immun 7 : 568–575. [Google Scholar]
  10. Awandare GA, Ouma Y, Ouma C, Were T, Otieno R, Keller CC, Davenport GC, Hittner JB, Vulule J, Ferrell R, Ong’echa JM, Perkins DJ, 2007. Role of monocyte-acquired hemozoin in suppression of macrophage migration inhibitory factor in children with severe malarial anemia. Infect Immun 75 : 201–210. [Google Scholar]
  11. Calandra T, Spiegel LA, Metz CN, Bucala R, 1998. Macrophage migration inhibitory factor is a critical mediator of the activation of immune cells by exotoxins of Gram-positive bacteria. Proc Natl Acad Sci U S A 95 : 11383–11388. [Google Scholar]
  12. Koebernick H, Grode L, David JR, Rohde W, Rolph MS, Mittrucker HW, Kaufmann SH, 2002. Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium. Proc Natl Acad Sci U S A 99 : 13681– 13686. [Google Scholar]
  13. Juttner S, Bernhagen J, Metz CN, Rollinghoff M, Bucala R, Gessner A, 1998. Migration inhibitory factor induces killing of Leishmania major by macrophages: dependence on reactive nitrogen intermediates and endogenous TNF-alpha. J Immunol 161 : 2383–2390. [Google Scholar]
  14. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R, 1993. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365 : 756–759. [Google Scholar]
  15. Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, Heumann D, Mannel D, Bucala R, Glauser MP, 2000. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med 6 : 164–170. [Google Scholar]
  16. Reyes JL, Terrazas LI, Espinoza B, Cruz-Robles D, Soto V, Rivera-Montoya I, Gomez-Garcia L, Snider H, Satoskar AR, Rodriguez-Sosa M, 2006. Macrophage migration inhibitory factor contributes to host defense against acute Trypanosoma cruzi infection. Infect Immun 74 : 3170–3179. [Google Scholar]
  17. Calandra T, Roger T, 2003. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 3 : 791–800. [Google Scholar]
  18. Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, Gemsa D, Donnelly T, Bucala R, 1996. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci U S A 93 : 7849–7854. [Google Scholar]
  19. Chaisavaneeyakorn S, Moore JM, Othoro C, Otieno J, Chaiyaroj SC, Shi YP, Nahlen BL, Lal AA, Udhayakumar V, 2002. Immunity to placental malaria. IV. Placental malaria is associated with up-regulation of macrophage migration inhibitory factor in intervillous blood. J Infect Dis 186 : 1371–1375. [Google Scholar]
  20. Chaiyaroj SC, Rutta AS, Muenthaisong K, Watkins P, Na Ubol M, Looareesuwan S, 2004. Reduced levels of transforming growth factor-beta1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria. Acta Trop 89 : 319–327. [Google Scholar]
  21. Martiney JA, Sherry B, Metz CN, Espinoza M, Ferrer AS, Calandra T, Broxmeyer HE, Bucala R, 2000. Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chabaudi-infected erythrocytes: possible role in the pathogenesis of malarial anemia. Infect Immun 68 : 2259–2267. [Google Scholar]
  22. McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A, McDonald C, Thuma P, Gordeuk VR, Metz CN, Mitchell R, Keefer J, David J, Leng L, Bucala R, 2006. A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia. J Exp Med 203 : 1185–1196. [Google Scholar]
  23. Perkins DJ, Kremsner PG, Schmid D, Misukonis MA, Kelly MA, Weinberg JB, 1999. Blood mononuclear cell nitric oxide production and plasma cytokine levels in healthy Gabonese children with prior mild or severe malaria. Infect Immun 67 : 4977–4981. [Google Scholar]
  24. Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG, 1998. Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarènè, Gabon. Trans R Soc Trop Med Hyg 92 : 110–114. [Google Scholar]
  25. Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG, 1998. Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 351 : 265–266. [Google Scholar]
  26. Weinberg JB, Muscato JJ, Niedel JE, 1981. Monocyte chemotactic peptide receptor. Functional characteristics and ligand-induced regulation. J Clin Invest 68 : 621–630. [Google Scholar]
  27. Bernhagen J, Calandra T, Bucala R, 1998. Regulation of the immune response by macrophage migration inhibitory factor: biological and structural features. J Mol Med 76 : 151–161. [Google Scholar]
  28. Perkins DJ, Weinberg JB, Kremsner PG, 2000. Reduced interleukin-12 and transforming growth factor-beta1 in severe childhood malaria: relationship of cytokine balance with disease severity. J Infect Dis 182 : 988–992. [Google Scholar]
  29. Luty AJ, Perkins DJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG, 2000. Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 68 : 3909–3915. [Google Scholar]
  30. Crutcher JM, Stevenson MM, Sedegah M, Hoffman SL, 1995. Interleukin-12 and malaria. Res Immunol 146 : 552–559. [Google Scholar]
  31. Chang KH, Stevenson MM, 2004. Malarial anaemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malaria. Int J Parasitol 34 : 1501–1516. [Google Scholar]
  32. Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M, Stevens A, Shelley E, Lamb R, Ollier WE, Thomson W, Ray D, 2002. Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis. Arthritis Rheum 46 : 2402–2409. [Google Scholar]
  33. Donn R, Alourfi Z, Zeggini E, Lamb R, Jury F, Lunt M, Meazza C, De Benedetti F, Thomson W, Ray D, 2004. A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis. Arthritis Rheum 50 : 1604–1610. [Google Scholar]
  34. Donn RP, Shelley E, Ollier WE, Thomson W, 2001. A novel 5′-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 44 : 1782–1785. [Google Scholar]
  35. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, Wolfe F, Gregersen PK, Bucala R, 2002. A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes Immun 3 : 170–176. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2007.76.1033
Loading
/content/journals/10.4269/ajtmh.2007.76.1033
Loading

Data & Media loading...

  • Received : 10 Oct 2006
  • Accepted : 17 Feb 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error