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Integrin αDβ2 influences cerebral edema, leukocyte accumulation and neurologic outcomes in experimental severe malaria.
- Source :
-
PloS one [PLoS One] 2019 Dec 23; Vol. 14 (12), pp. e0224610. Date of Electronic Publication: 2019 Dec 23 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Blood-Brain Barrier metabolism
Brain metabolism
Brain Edema metabolism
Brain Edema physiopathology
CD11 Antigens physiology
Chloroquine metabolism
Disease Models, Animal
Inflammation metabolism
Integrin alpha Chains physiology
Integrins immunology
Integrins metabolism
Leukocyte Count
Leukocytes metabolism
Leukocytes physiology
Macrophages metabolism
Malaria genetics
Malaria, Cerebral immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasmodium berghei metabolism
CD11 Antigens metabolism
Integrin alpha Chains metabolism
Malaria physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31869339
- Full Text :
- https://doi.org/10.1371/journal.pone.0224610