Nitric Oxide Participation in the Fungicidal Mechanism of Gamma Interferon-Activated Murine Macrophages against<i>Paracoccidioides brasiliensis</i>Conidia

González, Ángel; Gregori, Waldemar de; Velez, Diana; Restrepo, Ángela; Cano, Luz Elena

doi:10.1128/iai.68.5.2546-2552.2000

Cited by 133 publications

(117 citation statements)

References 43 publications

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“…These data suggest that regardless of the mouse strain, NO plays an essential role in the control of fungal dissemination. Our results confirm previous reports showing that NO is able to kill fungus and hence control parasite multiplication (6,7). In addition, we show that paradoxically, macrophages from susceptible mice produce very high levels of NO.…”

Section: Figuresupporting

confidence: 93%

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Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

Nascimento

Calich

Rodríguez

et al. 2002

The Journal of Immunology

127

107

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Using a murine model of susceptibility and resistance to paracoccidioidomycosis, we have previously demonstrated that immunosuppression occurs in susceptible (B10.A), but not in resistant (A/Sn), mouse strains. Accumulating evidence shows that NO is involved in the induction of T cell immunosuppression during infection as well as in the killing of Paracoccidioides brasiliensis. In the present work, we focused on NO and other macrophage products that could be associated with resistance or susceptibility to paracoccidioidomycosis. A striking difference was related to NO and TNF production. Macrophages from B10.A mice produced high and persistent NO levels, while in A/Sn animals, TNF production predominated. In in vitro cultures, P. brasiliensis-infected macrophages from A/Sn mice also produced large amounts of TNF, while B10.A macrophages only produced NO. TNF production by B10.A macrophages appeared to be suppressed by NO, because the addition of aminoguanidine sulfate, an inducible NO synthase (NOS2) inhibitor, resulted in TNF production. These results suggested that enhanced TNF or NO production is associated with resistance and susceptibility, respectively. However, regardless of the mouse strain, NOS2-deficient or aminoguanidine sulfate-treated mice presented extensive tissue lesions with increased fungal load in lungs and liver compared with their controls. We conclude that NOS2-derived NO is essential for resistance to paracoccidioidomycosis, but overproduction is associated with susceptibility.

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Section: Figuresupporting

confidence: 93%

“…Although NO production is involved in Pb killing (6), it can also be involved in immunosuppression, because NO inhibits lymphoproliferation, TNF-␣ production, and MHC class II molecule expression (7,8).…”

mentioning

confidence: 99%

Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

Nascimento

Calich

Rodríguez

et al. 2002

The Journal of Immunology

127

107

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“…In addition, it has been demonstrated that macrophages exert a fungicidal mechanism independent of oxidative burst products, but dependent on nitric oxide (NO) production [111,112]. However, in vivo the role of these effector molecules against P. brasiliensis has not been elucidated.…”

Section: Molecules Participating In Fungicidal Mechanismsmentioning

confidence: 99%

“…In vitro, our group has shown that IFN-c-activated peritoneal murine macrophages have a fungicidal effect against P. brasiliensis conidia, and that such effect depends on NO production [112]. This mechanism has been elucidated proposing that once in the cytoplasm, IFN-c attaches to its proper macrophage receptor inducing nuclear factor (NF)-jB production, thus prompting expression of the inducible nitric oxide synthase (iNOS) with activation of the L-arginine-nitric oxide pathway, and subsequent NO production as early as 18-24 h post-challenge [118].…”

Section: Expression Of Inos and Nitric Oxide Productionmentioning

confidence: 99%

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

2008

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“…Furthermore, studies in animal models have been described in which IFN--activated macrophages represent one of the most important mechanisms against this pathogen and induce a fungicidal effect 4 8 . This process is nitric-oxide dependent 11 .…”

Section: Discussionmentioning

confidence: 99%

Kinetics of IFN-gamma, TNF-alpha, IL-10 and IL-4 production by mononuclear cells stimulated with gp43 peptides, in patients cured of paracoccidioidomycosis

Sadahiro

Diogo

Oshiro

et al. 2007

Rev. Soc. Bras. Med. Trop.

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Nitric Oxide Participation in the Fungicidal Mechanism of Gamma Interferon-Activated Murine Macrophages againstParacoccidioides brasiliensisConidia

Cited by 133 publications

References 43 publications

Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

Dual Role for Nitric Oxide in Paracoccidioidomycosis: Essential for Resistance, but Overproduction Associated with Susceptibility

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

Kinetics of IFN-gamma, TNF-alpha, IL-10 and IL-4 production by mononuclear cells stimulated with gp43 peptides, in patients cured of paracoccidioidomycosis

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