Expression of hypoxia-inducible factor-1α in the cutaneous lesions of BALB/c mice infected with Leishmania amazonensis

Arrais-Silva, Wagner Welber; Paffaro, Valdemar A.; Yamada, Áureo T.; Giorgio, Selma

doi:10.1016/j.yexmp.2004.09.002

Cited by 43 publications

(44 citation statements)

References 21 publications

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“…During infections with the intracellular parasites Leishmania sp., Schistosoma mansoni, and Trypanosoma sp., Arg1 expression/activity was induced concomitantly with increasing parasite load (31,(53)(54)(55). Moreover, Arg1-expressing cells accumulate in and around S. mansoni granulomas (30,55,56) and in skin lesions from patients who have cutaneous leishmaniasis (57); these lesions often are necrotic and hypoxic (58,59). In murine S. mansoni infection, Arg1-expressing macrophages restrain Th2 cytokinedriven inflammation and fibrosis (30,60).…”

Section: Discussionmentioning

confidence: 99%

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Duque-Correa¹,

Kühl

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

109

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Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -uninfected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via L-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes L-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granuloma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hypoxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia.

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Section: Discussionmentioning

confidence: 99%

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Duque-Correa¹,

Kühl

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

109

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“…Several characteristics reveal the presence of a hypoxic microenvironment in lesions (50) and indicate that macrophages exposed to hypoxia showed a reduction in the percentage of infected cells and the number of intracellular parasites/cell BA125Ind/mLaVSP1 strain were loaded in these gels. LaVSP1 expressions were quantified by Western blotting using rabbit antisera directed against T. brucei VSP1 (28).…”

Section: Implication Of Lavsp In the Regulation Of The Polyphosphate mentioning

confidence: 99%

A Soluble Pyrophosphatase, a Key Enzyme for Polyphosphate Metabolism in Leishmania

Espiau

Lemercier

Ambit

et al. 2006

Journal of Biological Chemistry

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“…Thus, similar knowledge could help to determine the relevance of different host mediators in relation to leishmaniasis control or exacerbation and their predictive value. Recently, our group showed that mice cutaneous lesions present hypoxic areas, i.e., low oxygen tension in the diseased tissue [7,9]. In addition, infected macrophages from lesions accumulate HIF-1a and HIF-2a [7].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Araújo

Giorgio

2015

Arch Dermatol Res

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Leishmanioses are chronic parasitic diseases and host responses are associated with pro- or anti-inflammatory cytokines involved, respectively, in the control or exacerbation of infection. The relevance of other inflammatory mediators and stress markers has not been widely studied and there is a need to search for biomarkers to leishmaniasis. In this work, the stress and inflammatory molecules p38 mitogen-activated protein kinase, cyclooxygenase-2, migration inhibitory factor, macrophage inflammatory protein 2, heat shock protein 70 kDa, vascular endothelial factor (VEGF), hypoxia-inducible factors (HIF-1α and HIF-2α), heme oxygenase and galectin-3 expression were assessed immunohistochemically in self-controlled lesions in C57BL/6 mice and severe lesions in Balb/c mice infected with Leishmania amazonensis. The results indicated that the majority of molecules were expressed in the cutaneous lesions of both C57BL/6 and Balb/c mice during various phases of infection, suggesting no obvious correlation between the stress and inflammatory molecule expression and the control/exacerbation of leishmanial lesions. However, the cytokine VEGF was only detected in C57BL/6 footpad lesions and small lesions in Balb/c mice treated with antimonial pentavalent. These findings suggest that VEGF expression could be a predictive factor for murine leishmanial control, a hypothesis that should be tested in human leishmaniosis.

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Expression of hypoxia-inducible factor-1α in the cutaneous lesions of BALB/c mice infected with Leishmania amazonensis

Cited by 43 publications

References 21 publications

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

A Soluble Pyrophosphatase, a Key Enzyme for Polyphosphate Metabolism in Leishmania

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

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