Human immune responses to Plasmodium falciparum infection: Molecular evidence for a suboptimal THαβ and TH17 bias over ideal and effective traditional TH1 immune response

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Abstract

Background: Using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, NF-κB, TNF, p38-MAPK, and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum. Methods. This analysis reports herein further studies based on time-course microarray analysis with focus on malaria-induced host immune response. Results: The results show that in early malaria, selected immune response-related genes were up-regulated including α β and γ interferon-related genes, as well as genes of IL-15, CD36, chemokines (CXCL10, CCL2, S100A8/9, CXCL9, and CXCL11), TRAIL and IgG Fc receptors. During acute febrile malaria, up-regulated genes included α β and γ interferon-related genes, IL-8, IL-1b IL-10 downstream genes, TGFB1, oncostatin-M, chemokines, IgG Fc receptors, ADCC signalling, complement-related genes, granzymes, NK cell killer/inhibitory receptors and Fas antigen. During recovery, genes for NK receptorsand granzymes/perforin were up-regulated. When viewed in terms of immune response type, malaria infection appeared to induce a mixed TH1 response, in which α and β interferon-driven responses appear to predominate over the more classic IL-12 driven pathway. In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum. Gene markers of TH17 (neutrophil-related genes, TGFB1 and IL-6 family (oncostatin-M)) and THαβ (IFN-γ and NK cytotoxicity and ADCC gene) immune response were up-regulated. Initiation of THαβ immune response was associated with an IFN-αβ response, which ultimately resulted in moderate-mild IFN-γ achieved via a pathway different from the more classic IL-12 TH1 pattern. Conclusions: Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response. © 2013 Hu; licensee BioMed Central Ltd.

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Hu, W. C. (2013). Human immune responses to Plasmodium falciparum infection: Molecular evidence for a suboptimal THαβ and TH17 bias over ideal and effective traditional TH1 immune response. Malaria Journal, 12(1). https://doi.org/10.1186/1475-2875-12-392

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