Neutrophil Paralysis in Plasmodium vivax Malaria

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.

National Institutes of Health

National Institutes of Health [R21 AI080907, RO1 AI079293]

Malaria Network [CNPq-555646/2009-2/FAPEMIG/MS-CBB-APQ-01153-10]

Malaria Network

National Institute of Science and Technology for Vaccines

National Institute of Science and Technology for Vaccines [CNPq-573547/2008-4/FAPEMIG/MS-CBB-APQ 00077-09]

Program for Technological Development in Tools for Health from Fundacao Oswaldo Cruz [PDTIS-FIOCRUZ-RVR22]

Program for Technological Development in Tools for Health from Fundacao Oswaldo Cruz