scholarly journals X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Israel Diniz-Lima ◽  
Pablo Rodrigo da Rosa ◽  
Elias Barbosa da Silva-Junior ◽  
Joyce Cristina Guimarães-de-Oliveira ◽  
Elisangela Oliveira de Freitas ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Fungal Infections ◽  
Humoral Response ◽  
Cryptococcus Gattii ◽  
Opportunistic Disease ◽  
Fungal Load ◽  
Natural Igm ◽  
The Brain ◽  
Chronic Lung Infection

AbstractCryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.

scholarly journals IFN-γ mediated signaling improves fungal clearance in experimental pulmonary mucormycosis.

2021 ◽  
Author(s):  
Amanda Ribeiro dos Santos ◽  
Thais Fernanda Fraga-Silva ◽  
Débora de Fátima Almeida Donanzam ◽  
Rodolfo Ferreira dos Santos ◽  
Angela C. Finato ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Mouse Strains ◽  
Pulmonary Mucormycosis ◽  
Adaptive Immune ◽  
Swiss Mice ◽  
Fungal Load ◽  
Ifn Γ ◽  
First Time ◽  
The Brain

Abstract We established three immunocompetent murine models of pulmonary mucormycosis to determine the involvement of the adaptive immune response in host resistance in pulmonary mucormycosis, a rapidly fatal disease caused mainly by Rhizopus spp. Immunocompetent BALB/c, C57BL/6, and Swiss mice were inoculated with R. oryzae via the intratracheal route. The inoculation resulted in an angioinvasive infection that spread to the brain, spleen, kidney, and liver. After 7 and 30 days of R. oryzae infection, C57BL/6 and BALB/c mice showed the lowest fungal load and highest production of IFN-γ and IL-2 by splenocytes, respectively. Swiss mice showed a higher fungal load 30 days p.i. and was associated with a weak development of the Th-1 profile. To confirm our findings, R. oryzae-infected IFN-γ-/- mice were evaluated after 60 days, where the mice still showed viable fungi in the lungs. This study showed, for the first time, that pulmonary mucormycosis in three widely used mouse strains resulted in an acute fungal dissemination without immunosuppression whose outcome varies according to the genetic background of the mice . We also identified the partial role of IFN-γ in the efficient elimination of R. oryzae during pulmonary infection.

Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans

2006 ◽  
Vol 55 (9) ◽  
pp. 1291-1299 ◽  
Author(s):  
Yasuaki Aratani ◽  
Fumiaki Kura ◽  
Haruo Watanabe ◽  
Hisayoshi Akagawa ◽  
Yukie Takano ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Pulmonary Infection ◽  
Severe Pneumonia ◽  
Oxygen Species ◽  
Wild Type ◽  
Hypohalous Acids ◽  
The Brain ◽  
Oxidative System

The in vivo contribution of reactive oxygen species produced by neutrophils against Cryptococcus infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from H2O2. This study investigated the role of MPO in immunological defence against Cryptococcus neoformans in an MPO-deficient (MPO−/−) mouse model. The survival of MPO−/− mice infected either intranasally or intravenously with C. neoformans was lower than that of identically challenged wild-type mice. The MPO−/− mice that received intranasal injection of C. neoformans had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO−/− mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)-γ than wild-type mice, suggesting a weak Th1 response in the MPO−/− mice to C. neoformans. Pathologically, the MPO−/− mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1α/β in the lungs. In addition, in MPO−/− mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-derived cytokine (KC) level in the brain of infected MPO−/− mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO−/− mice compared to wild-type, suggesting decreased resistance to C. neoformans not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.

scholarly journals SCH 56592, Amphotericin B, or Itraconazole Therapy of Experimental Murine Cerebral Phaeohyphomycosis Due toRamichloridium obovoideum (“Ramichloridium mackenziei”)

2000 ◽  
Vol 44 (5) ◽  
pp. 1159-1162 ◽  
Author(s):  
Hail M. Al-Abdely ◽  
Laura Najvar ◽  
Rosie Bocanegra ◽  
Annette Fothergill ◽  
David Loebenberg ◽  
...  
Keyword(s):  
Middle East ◽  
Brain Tissue ◽  
Amphotericin B ◽  
The Other ◽  
Fungal Burden ◽  
Fungal Strains ◽  
Fungal Load ◽  
The Brain

ABSTRACT Ramichloridium obovoideum (“Ramichloridium makenziei”) is a rare cause of lethal cerebral phaeohyphomycosis. It has been, so far, geographically restricted to the Middle East. BALB/c mice were inoculated with two strains ofR. obovoideum intracranially. Therapy with amphotericin B, itraconazole, or the investigational triazole SCH 56592 was conducted for 10 days. Half the mice were monitored for survival and half were killed for determination of the fungal load in brain tissue. Recipients of SCH 56592 had significantly prolonged survival and lower brain fungal burden, and this result was found for mice infected with both of the fungal strains tested. Itraconazole reduced the brain fungal load in mice infected with one strain but not the other, while amphotericin B had no effect on brain fungal concentrations. This study indicates a possible role of SCH 56592 in the treatment of the serious cerebral phaeohyphomycosis due to R. obovoideum.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

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