Integrin αDβ2 influences cerebral edema, leukocyte accumulation and neurologic outcomes in experimental severe malaria

Autoři: Isaclaudia G. de Azevedo-Quintanilha aff001;  Adriana Vieira-de-Abreu aff001;  André C. Ferreira aff001;  Patricia A. Reis aff001;  Tathiany I. Silva aff001;  Danielle de O. Nascimento aff001;  Robert A. Campbell aff002;  Vanessa Estato aff001;  Andrew S. Weyrich aff002;  Patrícia T. Bozza aff001;  Guy A. Zimmerman aff002;  Hugo C. Castro-Faria-Neto aff001
Působiště autorů: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil aff001;  Department of Internal Medicine and Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the αD subunit (αD-/-) of the αDβ2 integrin, which is expressed on key leukocyte subsets in mice and humans, leads to absent expression of the integrin heterodimer on murine macrophages and reduces mortality in mice infected with Plasmodium berghei ANKA (P. berghei ANKA). To further identify mechanisms involved in the protective effect of αD deletion in this model of severe malaria we examined wild type C57BL/6 (WT) and αD-/- mice after P. berghei ANKA infection and found that vessel plugging and leukocyte infiltration were significantly decreased in the brains of αD-/- animals. Intravital microscopy demonstrated decreased rolling and adhesion of leukocytes in cerebral vessels of αD-/- mice. Flow cytometry analysis showed decreased T-lymphocyte accumulation in the brains of infected αD-/- animals. Evans blue dye exclusion assays demonstrated significantly less dye extravasation in the brains of αD-/- mice, indicating preserved blood-brain barrier integrity. WT mice that were salvaged from P. berghei ANKA infection by treatment with chloroquine had impaired aversive memory, which was not observed in αD-/- mice. We conclude that deletion of integrin αDβ2 alters the natural course of experimental severe malaria, demonstrating previously unrecognized activities of a key leukocyte integrin in immune-inflammatory responses that mediate cerebral involvement.

Klíčová slova:

Cerebral malaria – Inflammation – Integrins – Malaria – Mouse models – Plasmodium – T cells – White blood cells


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