Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/2795
Title: Leishmania infection impairs β1-integrin function and chemokine receptor expression in mononuclear phagocytes
Authors: Pinheiro Junior, Nathanael F
Hermida, Micely D' El Rei
Macedo, Mariana P
Mengele Junior, José Orivaldo
Bafica, Andre Luiz Barbosa
dosSantos, Washington Luis Conrado
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / NIAID, National Institutes of Health. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, Maryland, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil
Abstract: 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 CD11bhi 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.
Keywords: Leishmania
Infection
Chemokines
keywords: Leishmania
Infecção
Quimiocinas
DeCS: Animais
Antígenos CD29
Adesão Celular
Leishmania braziliensis
Leishmaniose Cutânea
Macrófagos Peritoneais
Camundongos
Camundongos Endogâmicos BALB C
Receptores de Quimiocinas
Issue Date: 2006
Publisher: American Society for Microbiology
Citation: PINHEIRO JUNIOR, N. F. et al. Leishmania infection impairs beta1-integrin function and chemokine receptor expression in mononuclear phagocytes. Infection and Immunity, v.74, n.7, p.3912–3921, jul. 2006.
Description: Agradecemos a Lain C. Pontes-de-Carvalho, a Claudia Ida Brodskyn (ambos da FIOCRUZ, Centro de Pesquisa Gonçalo Moniz), e Antonio Rothfuchs (NIH / NIAID) pela revisão cuidadosa e as sugestões para o manuscrito.
DOI: 10.1128/IAI.02103-05
ISSN: 0019-9567
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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