Leishmania infection modulates beta-1 integrin activation and alters the kinetics of monocyte spreading over fibronectin
Contact with Leishmania leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coa...
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Veröffentlicht in: | Scientific reports 2015-08, Vol.5 (1), p.12862-12862, Article 12862 |
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Sprache: | eng |
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Zusammenfassung: | Contact with
Leishmania
leads to a decreases in mononuclear phagocyte adherence to connective tissue. In this work, we studied the early stages of bond formation between VLA4 and fibronectin, measured the kinetics of membrane alignment and the monocyte cytoplasm spreading area over a fibronectin-coated surface and studied the expression of high affinity integrin epitope in uninfected and
Leishmania
-infected human monocytes. Our results show that the initial VLA4-mediated interaction of
Leishmania
-infected monocyte with a fibronectin-coated surface is preserved, however, the later stage, leukocyte spreading over the substrate is abrogated in
Leishmania
-infected cells. The median of spreading area was 72 [55–89] μm
2
for uninfected and 41 [34–51] μm
2
for
Leishmania
-infected monocyte. This cytoplasm spread was inhibited using an anti-VLA4 blocking antibody. After the initial contact with the fibronectrin-coated surface, uninfected monocyte quickly spread the cytoplasm at a 15 μm
2
s
−1
ratio whilst
Leishmania
-infected monocytes only made small contacts at a 5.5 μm
2
s
−1
ratio. The expression of high affinity epitope by VLA4 (from 39 ± 21% to 14 ± 3%); and LFA1 (from 37 ± 32% to 18 ± 16%) molecules was reduced in
Leishmania
-infected monocytes. These changes in phagocyte function may be important for parasite dissemination and distribution of lesions in leishmaniasis. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/srep12862 |