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

Hu WC - Malar. J. (2013)

Bottom Line: In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum.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.Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA. lukluk73_2006@yahoo.com.tw.

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 receptors and 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.

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Related in: MedlinePlus

IL-12 centred network analysis. IL-12 centred pathway analysis. Network analysis was performed by using IL-12 as the central nodes. This study used software to select IL-12 related genes from the gene list. Only four IL-12A/IL12B related genes were selected.
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Figure 4: IL-12 centred network analysis. IL-12 centred pathway analysis. Network analysis was performed by using IL-12 as the central nodes. This study used software to select IL-12 related genes from the gene list. Only four IL-12A/IL12B related genes were selected.

Mentions: Pathway analysis was conducted to explore immunological genetic circuitry during malaria infection. This study selected IL-4, IL-12, TGFB1/IL-6, IL-17, IFN-α/β as the central gene markers to explore possible networking among the 2,894 genes under analysis in this study. This study was able to identify only a few up-regulated genes in this cluster that centred on IL-4 (Figure 3) or IL-12 (Figure 4). In contrast, gene networks centred on TGFB1/IL6, IL-17 (Figure 5), or IFN-αβ (Figure 3) were more dramatically altered during the malaria disease cycle. These results further support a model for malaria immune response in which IL-17/IFN-alpha/beta plays a more central regulatory role than IL-4 and IL-12. Figure 6 shows a sketch of the major pathways of host immune response that are felt to play a role in recovery from malaria based on the observations made in this study, as well as those made by other investigators in previous research. The changes in their expression levels during the early, acute and recovery stages of P. falciparum infection are summarized in Figure 1. As shown in Figures 1, 7, 8 and 9, the expression of genes related to TH2 immune response were unchanged following malaria infection, with most changes occurring in genes related to the TH17 and THαβ driven pathway of anti-malaria immune response.


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

Hu WC - Malar. J. (2013)

IL-12 centred network analysis. IL-12 centred pathway analysis. Network analysis was performed by using IL-12 as the central nodes. This study used software to select IL-12 related genes from the gene list. Only four IL-12A/IL12B related genes were selected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928643&req=5

Figure 4: IL-12 centred network analysis. IL-12 centred pathway analysis. Network analysis was performed by using IL-12 as the central nodes. This study used software to select IL-12 related genes from the gene list. Only four IL-12A/IL12B related genes were selected.
Mentions: Pathway analysis was conducted to explore immunological genetic circuitry during malaria infection. This study selected IL-4, IL-12, TGFB1/IL-6, IL-17, IFN-α/β as the central gene markers to explore possible networking among the 2,894 genes under analysis in this study. This study was able to identify only a few up-regulated genes in this cluster that centred on IL-4 (Figure 3) or IL-12 (Figure 4). In contrast, gene networks centred on TGFB1/IL6, IL-17 (Figure 5), or IFN-αβ (Figure 3) were more dramatically altered during the malaria disease cycle. These results further support a model for malaria immune response in which IL-17/IFN-alpha/beta plays a more central regulatory role than IL-4 and IL-12. Figure 6 shows a sketch of the major pathways of host immune response that are felt to play a role in recovery from malaria based on the observations made in this study, as well as those made by other investigators in previous research. The changes in their expression levels during the early, acute and recovery stages of P. falciparum infection are summarized in Figure 1. As shown in Figures 1, 7, 8 and 9, the expression of genes related to TH2 immune response were unchanged following malaria infection, with most changes occurring in genes related to the TH17 and THαβ driven pathway of anti-malaria immune response.

Bottom Line: In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum.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.Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA. lukluk73_2006@yahoo.com.tw.

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 receptors and 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.

Show MeSH
Related in: MedlinePlus