iNOS knock-out mice are not more susceptible to pulmonary paracoccidioidomycosis (2005)
- Authors:
- Autor USP: CALICH, VERA LUCIA GARCIA - ICB
- Unidade: ICB
- Assunto: IMUNOLOGIA
- Language: Inglês
- Abstract: Objectives: Inducible nitric oxide synthase (iNOS) is one key enzyme generating nitric oxide (NO) from L-arginine. iNOS derived NO is a mediator of unspecific host defense and central in the clearance of microbial and parasitic infections. The aim of this work was to investigate the role of NO in the acute and chronic phases of pulmonary PCM. Methods and Results: Wild Type (WT) and iNOS KO C57BL/6 mice were i.t. infected with 1x106 yeast cells of P. brasiliensis. Mice were sacrificed 48h, 2 and 10 weeks post infection and the severity of the disease determined by organ CFU counts and pulmonary histopathology. Cytokines and antibodies levels were also determined in these periods. At 48h both mouse strains showed similar fungal loads and cytokines levels in the lungs. However, at week 2 KO mice showed decreased fungal loads in the lungs (KO 4.55±0.86 log10; WT 5.23±0.29 log10) concomitant with high levels of pulmonary TNF-alpha (KO 5976.7±1954.3 pg/mL; WT 1656.2±445.81 pg/mL) and high amounts of hepatic cytokines (TNF-alpha, IFN-gamma, IL-2 and IL-4, p<0.05). Interestingly, compared with WT, at week 10, iNOS KO mice showed increased fungal burdens in the lungs (KO 5.99±0.79 log10; WT 4.64±0.8 log10). In addition, these mice produced increased levels of IgE, IgG1, IgG2a, IgG2b and IgA antibodies (p<0.01) and high levels of IFN-gamma, IL-4 and IL-5 in liver supernatants (p<0.05). iNOS KO mice presented inflammatory reaction composed by well-organized granulomas containingepithelioid cells and multinuclear giant cells, surrounding aggregated yeast cells, whereas WT lesions were less organized and affect most of pulmonary parenchyma. The more organized lesions of KO mice appear to compensate the higher fungal loads resulting in equivalent mortality rates of both mouse strains. Conclusions: iNOS deficiency regulates fungal loads and severity of pulmonary lesions leading to equivalent disease outcomes in WT and iNOS KO mice
- Imprenta:
- Publisher: Comissão de Cultura e Extensão Universitária do ICB/USP
- Publisher place: São Paulo
- Date published: 2005
- Source:
- Título: Resumos
- Conference titles: Congresso do Instituto de Ciências Biomédicas
-
ABNT
BERNARDINO, Simone e CALICH, Vera Lúcia Garcia. iNOS knock-out mice are not more susceptible to pulmonary paracoccidioidomycosis. 2005, Anais.. São Paulo: Comissão de Cultura e Extensão Universitária do ICB/USP, 2005. . Acesso em: 23 jan. 2026. -
APA
Bernardino, S., & Calich, V. L. G. (2005). iNOS knock-out mice are not more susceptible to pulmonary paracoccidioidomycosis. In Resumos. São Paulo: Comissão de Cultura e Extensão Universitária do ICB/USP. -
NLM
Bernardino S, Calich VLG. iNOS knock-out mice are not more susceptible to pulmonary paracoccidioidomycosis. Resumos. 2005 ;[citado 2026 jan. 23 ] -
Vancouver
Bernardino S, Calich VLG. iNOS knock-out mice are not more susceptible to pulmonary paracoccidioidomycosis. Resumos. 2005 ;[citado 2026 jan. 23 ] - Depletion of natural killer cells induces a more severe pulmonary paracoccidioidomycosis in athymic and euthymic BALB/C mice
- Mannose receptors play a different role in the activation of macrophages from resistant and susceptible mice to Paracoccidioides brasiliensis infection
- Role of CD4, CD8 T cells, IFN-gama and IL-12 in the protective immunity against murine pulmonary paracoccidioidomycosis (PCM)
- Paracoccidioides brasiliensis-TLR-4 interaction induces macrophage activation but results in more severe paracoccidioimycosis
- Genetic deficiency of CD28 costimulatory molecule results in more severe Paracoccicioidomycosis (PCM) associated with decreased antibodies and cytokines production
- Suceptible and resistant mice to p. brasiliensis infection use an indoleamine 2,3-dioxygenase mechanism to control fungal growth
- Mannose receptors play a distinct role in the interaction of p. Brasiliensis cells with murine macrophages of resistant and susceptible.
- IL-10 deficiency determines a better fungicidal ability associated with overproduction of IFN-? and nitric oxide by Paracoccidioides brasiliensis infected macrophages
- Paracoccidioides brasiliensis infection determines dendritic cells to differentiate to the plasmocytoid subpopulation which induces a more severe pulmonary infection when transferred to resistant mice
- Nitric oxide but not treg cells plays a major immunoregulatory role in a pulmonary model of fungal infection
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