LeishmaniaInfection Impairs β1-Integrin Function and Chemokine Receptor Expression in Mononuclear Phagocytes
- 1 July 2006
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 74 (7), 3912-3921
- https://doi.org/10.1128/iai.02103-05
Abstract
Leishmaniaspp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown thatLeishmaniainfection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r= −0.826,P= 0.003) and parasite burden (r= −0.917,P= 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition,P= 0.005) in phagocyte adhesion to connective tissue, induced byLeishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels,P> 0.05). In addition,Leishmaniainfection diminished cell adhesion to fibronectin (54.1 to 96.2%,P< 0.01), collagen (15.7 to 83.7%,P< 0.05), and laminin (59.1 to 82.2%,P< 0.05). The CD11bhisubpopulation was highly infected (49.6 to 97.3%). Calcium and Mg2+replacement by Mn2+, a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused byLeishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis.Keywords
This publication has 57 references indexed in Scilit:
- Leishmania majorModulates Chemokine and Chemokine Receptor Expression by Dendritic Cells and Affects Their Migratory CapacityInfection and Immunity, 2005
- A simple and reproducible method to obtain large numbers of axenic amastigotes of different Leishmania speciesZeitschrift für Parasitenkunde, 2002
- QBC® for the diagnosis of human and canine american visceral leishmaniasis: preliminary dataRevista da Sociedade Brasileira de Medicina Tropical, 2001
- Evolution of Lesion Formation, Parasitic Load, Immune Response, and Reservoir Potential in C57BL/6 Mice following High- and Low-Dose Challenge withLeishmania majorInfection and Immunity, 2000
- Sequential regulation of alpha 4 beta 1 and alpha 5 beta 1 integrin avidity by CC chemokines in monocytes: implications for transendothelial chemotaxis.The Journal of cell biology, 1996
- The C–C Chemokine MCP-1 Differentially Modulates the Avidity of β1 and β2 Integrins on T LymphocytesImmunity, 1996
- Effect of RANTES on Eosinophil Adhesion to Plates Coated with Recombinant Soluble Intercellular Adhesion Molecule-1 and Expression of β2-lntegrin Adhesion Molecules on EosinophilsInternational Archives of Allergy and Immunology, 1995
- Leishmania infantum Tropism: Strain genotype or host immune status?Parasitology Today, 1994
- Adhesion molecules in lesions of American cutaneous leishmaniasisExperimental Dermatology, 1994
- Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cellsEuropean Journal of Immunology, 1993