The association of IL-8-251T/A polymorphism with complicated malaria in Karbi Anglong district of Assam

Mahanta, Anusree; Kakati, Sanjeeb; Baruah, Satyabrat Malla Bujar

doi:10.1016/j.cyto.2013.11.001

Cited by 16 publications

(14 citation statements)

References 34 publications

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“…The negative correlation of IL‐8 with severity and death may well be because the dogs were all sampled late in the disease course and this cytokine may well have a much quicker kinetic and peak early on in the disease. Higher concentrations are associated with more complicated malaria and in sepsis . In human sepsis, early (within the first 3 days of disease) elevation of IL‐8 was strongly predictive of poor outcome, whilst levels decreased significantly by day 7 .…”

Section: Discussionmentioning

confidence: 99%

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Leisewitz

Goddard

Gier

et al. 2019

Parasite Immunology

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Aims Babesia rossi causes severe disease in dogs. Here, we describe the association between serum cytokine concentrations and disease severity. Methods Seventeen controls and 55 PCR confirmed B rossi‐infected dogs were included. Diseased dogs were subdivided into 23 critically ill and 32 relatively well cases. Serum concentrations of 11 cytokines and biochemical markers of disease severity were determined. Results Significant differences were detected for IL‐6, IL‐8, IL‐10, MCP‐1 and TNF‐α between the groups. Generally, the more complicated the disease, the more pro‐inflammatory the cytokine milieu. IL‐8 showed a reverse trend and was negatively correlated with disease severity. IL‐6, MCP‐1 and TNF‐α were also significantly higher in the dogs that died (n = 9) compared to the dogs that survived (n = 46). IL‐8 showed the opposite. MCP‐1 and TNF‐α were negatively correlated with biochemical markers of severity. Glucose was negatively correlated with IL‐6. Cortisol, peripheral parasite density and band neutrophil count were positively correlated, whilst thyroid hormone was negatively correlated with IL‐6, MCP‐1 and TNF‐α. Conclusions As in malaria and sepsis, B rossi infection induces a pro‐inflammatory cytokine storm that correlates with disease severity and adverse outcome. The multiplicity of cytokines involved argues for redundancy in the system once the disease is established.

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Section: Discussionmentioning

confidence: 99%

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Leisewitz

Goddard

Gier

et al. 2019

Parasite Immunology

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“…The detailed description of the study site and the study population used in this study have been previously described. 6,21 Briefly, malaria patients stratified into SM and UM based on the World Health Organisation guidelines were followed up in a longitudinal study by multiple sampling at the stages of active infection before treatment (day 0), parasite clearance (day 3) and resolution of clinical symptoms (day 7). After obtaining written informed consent from the participants, venous blood was collected in RNAlater (Ambion, Austin, TX, USA) from the patients for all the 3 days.…”

Section: Study Site Study Design and Subjectsmentioning

confidence: 99%

Lower expression of GATA3 and T‐bet correlates with downregulated IL‐10 in severe falciparum malaria

Mahanta

Baruah

2015

Clin & Trans Imm

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Interleukin (IL)-10, a non-redundant anti-inflammatory cytokine is produced by different cells and its production involves activation of cell-specific transcriptional regulatory machinery in response to specific pathogen. We have previously demonstrated downregulated levels of IL-10 in severe falciparum malaria. The present study investigated transcriptional regulation of IL-10 in severe malaria. Comparative expression analysis of cell-specific signalling proteins and transcription factors for IL-10 production during the stage of active infection and with resolution of parasitaemia was performed. Interestingly, T-bet and GATA3, the Th1 and Th2 transcription factors, respectively, were downregulated in severe malaria with fold change values of 0.59 and 0.86. Increase in the levels of both the factors with resolution of parasitaemia implicated a role for parasite in depressed levels of these factors. Further support for probable parasite manipulation of GATA3 was obtained from negative correlation of GATA3 with parasitaemia. In addition, a role for interferon-α in suppressing IL-10 transcription was evident from its negative correlation with GATA3 and IL-10 levels. In summary, IL-10 transcription in Th1 and Th2 is defective and appears to have major contribution to low levels in severe malaria.

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“…IL-8 levels may act as a preliminary identification of malaria in these individuals when blood parasitemia is sub-microscopic. Interestingly, we also found a positive correlation between plasma IL-8 levels and PMR, indicating that IL-8 is not only a marker of early infection but may also contribute to infection progression, and consequently disease severity, as supported by previous genetic and biochemical studies 248,249 .…”

Section: Discussionsupporting

confidence: 83%

Characterisation of anti-parasitic CD4+ T cell responses during malaria

Edwards¹

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1 AbstractThe CD4 + T cell response during malaria is critical for control of Plasmodium infection.Unfortunately, this response is commonly dysfunctional or absent in individuals living in malaria endemic regions, and current vaccination efforts have been unable to effectively overcome these short comings. Therefore, a better understanding of host immune responses during Plasmodium infection is required if we are to improve vaccine efficacy and promote long-lived protective immunity. To improve our understanding of the CD4 + T cell response, we assessed changes in the transcriptional profile of these cells, over the course of Plasmodium falciparum infection, in volunteers who had not previously been exposed toPlasmodium, who were taking part in controlled human malaria infection (CHMI) studies.Bioinformatic analysis identified CXCL8 expression as a biomarker of sub-microscopic infection. Additionally, the degree of CXCL8 expression was indicative of initial parasite growth rate. We also identified the emergence of a significant regulatory profile in the CD4 + T cell population which developed with drug-mediated clearance of infection. This profile included checkpoint inhibitors PD-1, LAG-3, TIM-3, and CTLA-4. The degree of PD-1 expression on putative Tr1 (CD49b+ LAG-3+) cells negatively correlated with initial parasite growth rate. However, only PD-1 blockade affected antigen specific expression of the Tr1 cell related cytokines IFNγ and IL-10 by peripheral blood mononuclear cells (PBMCs) from CHMI study volunteers. Another transcriptional change following drug-mediated control was down-regulation of the master transcription factor BACH2. BACH2 plays an important role in T cell homeostasis and facilitates the stability and function of the FOXP3 + regulatory T (Treg) cell population while modulating effector T cell differentiation. Using transgenic mice with T cell specific BACH2 deficiency we showed that BACH2 was an important intrinsic factor in CD4 + T cells during cell differentiation in vitro. In the context of experimental malaria and a second parasitic infection, visceral leishmaniasis (VL), we showed that T cell-specific BACH2 modulated Th2, Th17 and Tfh cell differentiation, and suppressed effector CD4 + T cell responses. However, BACH2 was also important for the expansion and/or maintenance of splenic Treg cells during parasitic infection. Using pathway analysis to further assess the Plasmodium induced change in the transcriptional profile of CD4 + T cells we identified differential regulation of the IL-10 Abstract 42325972 2 signalling pathway after drug-mediated clearance of infection. In a number of parasitic infections, IL-10 signalling is primarily mediated by a FOXP3 -IL-10-producing regulatory CD4 + T (Tr1) cell subset. Tr1 cell frequency has been positively correlated with chronic malaria exposure in Ugandan children, and in mouse models of VL and malaria. We recently reported that Tr1 cells suppressed anti-parasitic immune responses, but also played a key role in preventing immunopathology. To i...

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The association of IL-8-251T/A polymorphism with complicated malaria in Karbi Anglong district of Assam

Cited by 16 publications

References 34 publications

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

Lower expression of GATA3 and T‐bet correlates with downregulated IL‐10 in severe falciparum malaria

Characterisation of anti-parasitic CD4+ T cell responses during malaria

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