Effect of Hypoxia on Macrophage Infection by Leishmania Amazonensis

Colhone, Marcelle C.; Arrais-Silva, Wagner Welber; Picoli, Claudia; Giorgio, Selma

doi:10.1645/ge-3286

Cited by 39 publications

(68 citation statements)

References 30 publications

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“…Similarly to M. tuberculosis, the multiplication of the parasite Leishmania amazonensis in a human macrophage-like cell line and in dendritic cells is reduced at 5% oxygen tension (34,35), corroborating the impression that hypoxia favors the antimicrobial activity of macrophages. In contrast, one report demonstrates an opposite effect on epithelial cells (36).…”

Section: Discussionmentioning

confidence: 54%

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Nickel

Busch

Mayer

et al. 2012

The Journal of Immunology

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Low oxygen tension is a metabolic hallmark of chronic infection. To investigate the influence of hypoxia on macrophage biology, we analyzed the interaction between the intracellular pathogen Mycobacterium tuberculosis and primary human macrophages. Although the metabolic activity of extracellular M. tuberculosis was reduced at oxygen levels between 0.5 and 10%, the bacilli remained viable throughout the 4 d of culture. Phagocytosis of virulent M. tuberculosis and the pathogen-induced release of inflammatory cytokines by macrophages were not affected by oxygen levels as low as 1%. However, we detected the upregulation of an antimicrobial effector pathway mediated by the vitamin D receptor and human β defensin 2. This finding was functionally relevant, because intracellular mycobacterial growth was inhibited by 58 ± 8% at 1% O2. We conclude that a hypoxic microenvironment, which is characteristic of infected tissue, supports the efficacy of antimicrobial immunity, in part by the upregulation of the antimicrobial peptide human β defensin 2.

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Section: Discussionmentioning

confidence: 54%

Hypoxia Triggers the Expression of Human β Defensin 2 and Antimicrobial Activity against Mycobacterium tuberculosis in Human Macrophages

Nickel

Busch

Mayer

et al. 2012

The Journal of Immunology

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“…Phagocytosis efficiency has been reported to be increased by hypoxia. On one hand, the bactericidal capacity of macrophages in hypoxia is increased (33,58,59). On the other hand, hypoxia reoxygenation treatments increased in vivo Fc␥R-mediated phagocytosis (60).…”

Section: Discussionmentioning

confidence: 99%

Macrophage Oxygen Sensing Modulates Antigen Presentation and Phagocytic Functions Involving IFN-γ Production through the HIF-1α Transcription Factor

Acosta‐Iborra

Elorza

Olazabal

et al. 2009

The Journal of Immunology

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Low oxygen tension areas are found in inflamed or diseased tissues where hypoxic cells induce survival pathways by regulating the hypoxia-inducible transcription factor (HIF). Macrophages are essential regulators of inflammation and, therefore, we have analyzed their response to hypoxia. Murine peritoneal elicited macrophages cultured under hypoxia produced higher levels of IFN-␥ and IL-12 mRNA and protein than those cultured under normoxia. A similar IFN-␥ increment was obtained with in vivo models using macrophages from mice exposed to atmospheric hypoxia. Our studies showed that IFN-␥ induction was mediated through HIF-1␣ binding to its promoter on a new functional hypoxia response element. The requirement of HIF-␣ in the IFN-␥ induction was confirmed in RAW264.7 cells, where HIF-1␣ was knocked down, as well as in resident HIF-1␣ null macrophages. Moreover, Ag presentation capacity was enhanced in hypoxia through the up-regulation of costimulatory and Ag-presenting receptor expression. Hypoxic macrophages generated productive immune synapses with CD8 T cells that were more efficient for activation of TCR/CD3, CD3 and linker for activation of T cell phosphorylation, and T cell cytokine production. In addition, hypoxic macrophages bound opsonized particles with a higher efficiency, increasing their phagocytic uptake, through the upregulated expression of phagocytic receptors. These hypoxia-increased immune responses were markedly reduced in HIF-1␣-and in IFN-␥-silenced macrophages, indicating a link between HIF-1␣ and IFN-␥ in the functional responses of macrophages to hypoxia. Our data underscore an important role of hypoxia in the activation of macrophage cytokine production, Ag-presenting activity, and phagocytic activity due to an HIF-1␣-mediated increase in IFN-␥ levels.

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“…Macrophage infection with L. amazonensis -Primary mouse macrophages (5 × 10 5 /ml) were obtained from normal BALB/c mice by peritoneal washing, cultured on 24-well plates containing 13 mm diameter glass coverslips and infected with amastigotes (3:1 parasite/ host cell) for 1 h, as described previously (Colhone et al 2004). After the interaction period, the cultures were washed to remove extracellular parasites and incubated in the presence or absence of different concentrations of propolis or diluent (0.1% ethanol), at 37 o C in 5% CO 2 in air in a humidified incubator as established by Ayres et al (2006).…”

Section: Methodsmentioning

confidence: 99%

“…After the indicated periods of treatments, coverslips were fixed with methanol, stained with Giemsa, and examined under light microscope. Six hundred cells were counted per triplicate coverslip for the evaluation of the percentage of infected macrophages and the number of amastigotes per infected macrophage (Colhone et al 2004). The infection levels were quantified using a light microscopy at 1000 magnification.…”

Section: Methodsmentioning

confidence: 99%