On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Hojo-Souza, Natália Satchiko; Pereira, Dhelio Batista; Souza, Fernanda S. H.; Mendes, Tiago Antônio de Oliveira; Cardoso, Mariana M. B.; Tada, Mauro Shugiro; Zanini, Graziela Maria; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio; Bueno, Lilian Lacerda

doi:10.1186/s12936-017-1683-5

Cited by 22 publications

(28 citation statements)

References 46 publications

(91 reference statements)

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“…Parasitemia has being associated with increased levels of specific cytokines in vivax malaria 12 . Considering that rosetting levels were associated with parasitemia the role of plasmatic cytokines in rosetting was investigated.…”

Section: Resultsmentioning

confidence: 99%

“…However, parasitemia and IL-10 correlated with rosetting frequency. IL-10 has also been associated with previous malaria infection 12,29 , which could indicate that rosetting is also more frequent in individuals that were previously infected.…”

Section: Discussionmentioning

confidence: 99%

Rosettes integrity protects Plasmodium vivax of being phagocytized

Albrecht

Lopes

Silva

et al. 2020

Sci Rep

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Plasmodium vivax is the most prevalent cause of malaria outside of Africa. P. vivax biology and pathogenesis are still poorly understood. The role of one highly occurring phenotype in particular where infected reticulocytes cytoadhere to noninfected normocytes, forming rosettes, remains unknown. Here, using a range of ex vivo approaches, we showed that P. vivax rosetting rates were enhanced by plasma of infected patients and that total immunoglobulin M levels correlated with rosetting frequency. Moreover, rosetting rates were also correlated with parasitemia, IL-6 and IL-10 levels in infected patients. Transcriptomic analysis of peripheral leukocytes from P. vivax-infected patients with low or moderated rosetting rates identified differentially expressed genes related to human host phagocytosis pathway. In addition, phagocytosis assay showed that rosetting parasites were less phagocyted. Collectively, these results showed that rosette formation plays a role in host immune response by hampering leukocyte phagocytosis. Thus, these findings suggest that rosetting could be an effective P. vivax immune evasion strategy.

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“…and HBV coinfected individuals demonstrated elevated concentrations of IL-10 (eight-fold) and C-C Motif Chemokine Ligand 2 (CCL2) in comparison to those with P. vivax infection [14]. CCL2 has been reported to be produced by hepatocytes during HBV infection [40] and is related to P. vivax infection [41].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of and risk factors for Plasmodium spp. co-infection with hepatitis B virus: a systematic review and meta-analysis

Kotepui

2020

Malar J

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Background Plasmodium spp. and hepatitis B virus (HBV) are among the most common infectious diseases in underdeveloped countries. This study aimed to determine the prevalence of Plasmodium spp. and HBV co-infection in people living in endemic areas of both diseases and to assess the risk factors related to this co-infection. Methods The PubMed, Web of Science, and Scopus databases were searched. Observational cross-sectional studies and retrospective studies assessing the prevalence of Plasmodium species and HBV co-infection were examined. The methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale (NOS), a tool for assessing the quality of nonrandomized studies in meta-analyses, and heterogeneity among the included studies was assessed with Cochran's Q test and the I2 (inconsistency) statistic. The pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effects model, depending on the amount of heterogeneity there was among the included studies. The pooled odds ratio (OR) represented the difference in qualitative variables, whereas the pooled mean difference (MD) represented the difference in quantitative variables. Meta-analyses of the potential risk factors for Plasmodium spp. and HBV co-infection, including patient age and gender, were identified and represented as pooled odds ratios (OR) and 95% CIs. Publication bias among the included studies was assessed by visual inspection of a funnel plot to search for asymmetry. Results Twenty-two studies were included in the present systematic review and meta-analysis. Overall, the pooled prevalence estimate of Plasmodium spp. and HBV co-infection was 6% (95% CI 4–7%, Cochran's Q statistic < 0.001, I2: 95.8%), with prevalences of 10% in Gambia (95% CI: 8–12%, weight: 4.95%), 8% in Italy (95% CI 5–12%, weight: 3.8%), 7% in Nigeria (95% CI 4–10%, weight: 53.5%), and 4% in Brazil (95% CI 2–5%, weight: 19.9%). The pooled prevalence estimate of Plasmodium spp. and HBV co-infection was higher in studies published before 2015 (7%, 95% CI 4–9%, Cochran's Q statistic < 0.001, I2: 96%) than in those published since 2015 (3%, 95% CI 1–5%, Cochran's Q statistic < 0.001, I2: 81.3%). No difference in age and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and the Plasmodium monoinfection group (p: 0.48, OR: 1.33, 95% CI 0.60–2.96). No difference in gender and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and HBV co-infection group and the Plasmodium monoinfection group (p: 0.09, OR: 2.79, 95% CI 0.86–9.10). No differences in mean aspartate aminotransferase (AST), mean alanine aminotransferase (ALT), or mean total bilirubin levels were found (p > 0.05) between the Plasmodium spp. and HBV co-infection group and the Plasmodium monoinfection group. Conclusions The present study revealed the prevalence of Plasmodium spp. and HBV co-infection, which will help in understanding co-infection and designing treatment strategies. Future studies assessing the interaction between Plasmodium spp. and HBV are recommended.

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“…Decreased levels of IL-27 have been found in infants with severe falciparum malaria [26]. IL-27 levels are elevated in placental and cord blood compared with peripheral blood immediately following delivery in falciparum infected women [15], while no clear pattern was found during P. vivax malaria [27]. This is, however, the first report of IL-27 levels in adult patients with falciparum malaria demonstrating increased plasma levels as compared with healthy controls and HIV-infected patients with similar febrile illness, independent of co-infection with HIV.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria

et al. 2020

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Background: The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce. Methods: Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV-1 co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells and PBMC using hemozoin crystals. Samples were analyzed using enzyme immunoassays and quantitative PCR. Results: (i) IL-27 was markedly up-regulated in malaria patients compared with controls and HIV-infected patients without malaria, showing no relation to HIV co-infection. (ii) IL-27 was correlated with P. falciparum parasitemia and von Willebrand factor as a marker of endothelial activation, but not with disease severity. (iii) In vitro, IL-27 modulated the hemozoin-mediated cytokine response in endothelial cells and PBMC with enhancing effects on IL-6 and attenuating effects on IL-8. Conclusion: Our findings show that IL-27 is regulated during falciparum malaria, mediating both inflammatory and anti-inflammatory effects, potentially playing an immune-regulatory role during falciparum malaria.

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“…Monocytic acquisition of hemozoin suppresses RANTES production in children with malarial anaemia . Very recently, lower levels of RANTES/CCL5 have been shown to correlate with P. vivax infection also and effects of malaria infection result in HIV‐1 pathogenesis through CCR5 .…”

Section: Discussionmentioning

confidence: 99%

RANTES levels as a determinant of falciparum malaria severity or recovery

et al. 2017

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The study explored the role of differential RANTES concentrations, its receptor CCR5 expression and resulting immunomodulation in the pathogenesis and/or recovery from falciparum malaria. The study population included cases of uncomplicated malaria (UC-M, N=128, enrolled on follow-up basis), severe malaria (SM, N=25), and healthy controls (N=112). Serum RANTES and TNF-α levels were evaluated by ELISA. Monocyte levels and activation profile were studied by flow cytometry. Differential mRNA expression profile was studied by real-time PCR. Blood parasite count was evaluated by registered pathologists. RANTES concentration was significantly downregulated in SM cases compared to UC-M (P=.046) and controls (P<.001). Expression of monocyte marker mCD14, activation markers CCR5 and CD40, and downstream effector cytokine TNF-α was significantly higher in malaria cases compared to controls, in SM cases compared to UC-M. TNF-α expression correlated positively with CD40 and CCR5 expressions. Follow-up-based analysis showed that RANTES concentrations increased on recovery compared to baseline in UC-M cases (P=.106) and inversely correlated with malaria parasite load, mCD14, CCR5 and CD40, and TNF-α expressions. These findings suggest an important association of RANTES concentrations in Plasmodium falciparum malaria disease pathogenesis, as well as recovery, mediated through differential modulation and regulated activation of monocytes and cytokine TNF-α.

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On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Cited by 22 publications

References 46 publications

Rosettes integrity protects Plasmodium vivax of being phagocytized

Prevalence of and risk factors for Plasmodium spp. co-infection with hepatitis B virus: a systematic review and meta-analysis

Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria

RANTES levels as a determinant of falciparum malaria severity or recovery

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