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Neutrophil paralysis in Plasmodium vivax malaria.

Leoratti FM, Trevelin SC, Cunha FQ, Rocha BC, Costa PA, Gravina HD, Tada MS, Pereira DB, Golenbock DT, Antonelli LR, Gazzinelli RT - PLoS Negl Trop Dis (2012)

Bottom Line: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects.Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine.While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria.

Materials and methods: Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients.

Principal findings: Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8).

Conclusion: Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.

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Related in: MedlinePlus

GRK2 expression is enhanced in neutrophils during acute malaria.Neutrophils isolated from P. vivax-infected patients (closed circles; n = 11) or healthy donors (closed circles; n = 12) were stained for GRK2 and mean fluorescence intensity (MFI) of GRK2 was quantified (A). Representative fluorescence microscopy illustrating GRK2 expression in neutrophils from a healthy donor and a P. vivax-infected patient (B). Significant difference is indicated with p-values using unpaired t test.
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pntd-0001710-g006: GRK2 expression is enhanced in neutrophils during acute malaria.Neutrophils isolated from P. vivax-infected patients (closed circles; n = 11) or healthy donors (closed circles; n = 12) were stained for GRK2 and mean fluorescence intensity (MFI) of GRK2 was quantified (A). Representative fluorescence microscopy illustrating GRK2 expression in neutrophils from a healthy donor and a P. vivax-infected patient (B). Significant difference is indicated with p-values using unpaired t test.

Mentions: GRK2 has been described to down-modulate expression of chemokine receptors. Importantly, continuous and excessive activation of neutrophils results in an increased expression of GRKs, which phosphorylate G protein–coupled receptors (GPCR) leading to receptor desensitization [21]. GRK2 expression was measured by immunofluorescence in neutrophils purified from blood of P. vivax-infected patients and HD (median: 12.6; IQR: 4.7–23). Compared with HD, a significant increase in GRK2 expression was observed in neutrophils from P. vivax-infected patients (Figure 6A and 6B).


Neutrophil paralysis in Plasmodium vivax malaria.

Leoratti FM, Trevelin SC, Cunha FQ, Rocha BC, Costa PA, Gravina HD, Tada MS, Pereira DB, Golenbock DT, Antonelli LR, Gazzinelli RT - PLoS Negl Trop Dis (2012)

GRK2 expression is enhanced in neutrophils during acute malaria.Neutrophils isolated from P. vivax-infected patients (closed circles; n = 11) or healthy donors (closed circles; n = 12) were stained for GRK2 and mean fluorescence intensity (MFI) of GRK2 was quantified (A). Representative fluorescence microscopy illustrating GRK2 expression in neutrophils from a healthy donor and a P. vivax-infected patient (B). Significant difference is indicated with p-values using unpaired t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3383745&req=5

pntd-0001710-g006: GRK2 expression is enhanced in neutrophils during acute malaria.Neutrophils isolated from P. vivax-infected patients (closed circles; n = 11) or healthy donors (closed circles; n = 12) were stained for GRK2 and mean fluorescence intensity (MFI) of GRK2 was quantified (A). Representative fluorescence microscopy illustrating GRK2 expression in neutrophils from a healthy donor and a P. vivax-infected patient (B). Significant difference is indicated with p-values using unpaired t test.
Mentions: GRK2 has been described to down-modulate expression of chemokine receptors. Importantly, continuous and excessive activation of neutrophils results in an increased expression of GRKs, which phosphorylate G protein–coupled receptors (GPCR) leading to receptor desensitization [21]. GRK2 expression was measured by immunofluorescence in neutrophils purified from blood of P. vivax-infected patients and HD (median: 12.6; IQR: 4.7–23). Compared with HD, a significant increase in GRK2 expression was observed in neutrophils from P. vivax-infected patients (Figure 6A and 6B).

Bottom Line: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects.Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine.While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: The activation of innate immune responses by Plasmodium vivax results in activation of effector cells and an excessive production of pro-inflammatory cytokines that may culminate in deleterious effects. Here, we examined the activation and function of neutrophils during acute episodes of malaria.

Materials and methods: Blood samples were collected from P. vivax-infected patients at admission (day 0) and 30-45 days after treatment with chloroquine and primaquine. Expression of activation markers and cytokine levels produced by highly purified monocytes and neutrophils were measured by the Cytometric Bead Assay. Phagocytic activity, superoxide production, chemotaxis and the presence of G protein-coupled receptor (GRK2) were also evaluated in neutrophils from malaria patients.

Principal findings: Both monocytes and neutrophils from P. vivax-infected patients were highly activated. While monocytes were found to be the main source of cytokines in response to TLR ligands, neutrophils showed enhanced phagocytic activity and superoxide production. Interestingly, neutrophils from the malaria patients expressed high levels of GRK2, low levels of CXCR2, and displayed impaired chemotaxis towards IL-8 (CXCL8).

Conclusion: Activated neutrophils from malaria patients are a poor source of pro-inflammatory cytokines and display reduced chemotactic activity, suggesting a possible mechanism for an enhanced susceptibility to secondary bacterial infection during malaria.

Show MeSH
Related in: MedlinePlus