This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pinheiro, N. F. Articles by dos-Santos, W. L. C. Search for Related Content PubMed PubMed Citation Articles by Pinheiro, N. F., Jr. Articles by dos-Santos, W. L. C.

 Previous Article  |  Next Article 

Infection and Immunity, July 2006, p. 3912-3921, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.02103-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Leishmania Infection Impairs ß₁-Integrin Function and Chemokine Receptor Expression in Mononuclear Phagocytes

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil,¹ Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil,² Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland³

Received 30 December 2005/ Returned for modification 11 February 2006/ Accepted 6 April 2006

Leishmania spp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown that Leishmania infection 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 by Leishmania, 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, Leishmania infection 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 CD11b^hi subpopulation 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 by Leishmania. 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.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• Gregory, D. J., Sladek, R., Olivier, M., Matlashewski, G. (2008). Comparison of the Effects of Leishmania major or Leishmania donovani Infection on Macrophage Gene Expression. Infect. Immun. 76: 1186-1192 [Abstract] [Full Text]