Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line

Blasi, Elisabetta

doi:10.1016/0165-5728(95)00016-u

Cited by 73 publications

(67 citation statements)

References 30 publications

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“…Microglial cells are resident macrophage-like cells of the CNS (12) that have the ability to kill cryptococci in vitro (3,30). Because microglial cells are resident cells of the CNS, one might not expect to see changes in their numbers in the CNS as a result of infection; however, we observed a dramatic increase after i.c.…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, a defined growth medium consisting of 2% dextrose, 0.4 mM thiamine, 1% trace elements (0. 3 per liter of endotoxin-free water), 10 g of asparagine, 0.025 g of CaCl 2 , and 0.4 g of K 2 HPO 4 per liter of endotoxin-free water was prepared, and the pH was adjusted to 5.0. The medium was sterilized by autoclaving and inoculated with 10 9 yeast cells/liter, and the culture was incubated for 5 days at 30°C.…”

Section: Methodsmentioning

confidence: 99%

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Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Buchanan

Doyle

2000

Infect Immun

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The importance of cell-mediated immunity (CMI) and CD4؉ T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4 ؉ T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Buchanan

Doyle

2000

Infect Immun

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“…IFN-␥ has been demonstrated to enhance the anticryptococcal activity of murine microglial cells in vitro by inducing MHC class II expression and NO production (37)(38)(39). To determine whether IFN-␥ was an important mediator of anti-CD40 and IL-2 immunotherapy in the brain, the efficacy of anti-CD40/IL-2 treatment in IFN-␥ KO (GKO) mice were compared with WT mice.…”

Section: Ifn-␥ Signaling Is Required For the Protection Induced By Anmentioning

confidence: 99%

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Zhou

Gault

Kozel

et al. 2007

The Journal of Immunology

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The brain represents a significant barrier for protective immune responses in both infectious disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.

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“…It is clear from animal models of cryptococcosis that individual clinical and environmental C. neoformans strains differ in relative virulence (Vanbreuseghem, 1967;Hasenclever & Mitchell, 1960;Kwon-Chung et al, 1992;Blasi et al, 1992Blasi et al, , 1995Blackstock & Murphy, 1997;Curtis et al, 1994;Blackstock et al, 1999;Fries & Casadevall, 1998). Comparing two C. neoformans var.…”

Section: Introductionmentioning

confidence: 99%

Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors

et al. 2006

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Cryptococcus neoformans is a common cause of meningoencephalitis among AIDS patients. Several C. neoformans virulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the corrrelation of the virulence of 18 C. neoformans var. grubii isolates from AIDS patients with the expression of several well-described virulence factors. The LD 50 at 15 days after intracranial inoculation of ICR mice was <100 c.f.u. for 22 % of isolates, 100-1000 for 28 %, 1000-10 000 for 11 % and >20 000 for 39 %. Higher cryptococcal concentrations in brains were noted for isolates with lower LD 50 (P=0?002). In survival studies, no immunocompetent BALB/c mice (nu/") infected with 36LD 50 of three virulent isolates (LD 50 =62, 99, 1280) survived beyond 23 days, whereas 100 %, 90 % and 90 % of mice infected with 20 000 c.f.u. of three hypovirulent isolates (LD 50 >20 000) survived for 60 days (P<0?0001). Even among BALB/c nude (nu/nu) mice, survival rates over 60 days were 100 %, 70 % and 50 %, respectively, for the hypovirulent isolates. Growth rate at 37 6C and capsule size within brains correlated with LD 50 by univariate (P=0?0001 and 0?028, respectively) and multivariate (P=0?017 and 0?016, respectively) analyses. There was no correlation between LD 50 and capsule size in vitro, phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection by C. neoformans isolates of wide-ranging virulence, including isolates that are markedly hypovirulent. The virulence of a given isolate reflects a composite of factors rather than the contribution of a dominant factor. Growth at 37 6C and capsule size in vivo make particularly important contributions. INTRODUCTIONCryptococcus neoformans is a yeast-like fungus that is generally found in soil with a high content of avian guano or vegetative debris (Casadevall & Perfect, 1998;Mitchell & Perfect, 1995). Infections of humans, believed to be acquired by inhalation of small yeast cells or basidiospores, are often clinically silent. In fact, the most commonly recognized manifestation of cryptococcal disease (cryptococcosis) is not pneumonia but rather meningitis or meningoencephalitis. Cryptococcal central nervous system (CNS) infections and other forms of cryptococcosis are largely, but not exclusively, diseases of persons with AIDS or other immunosuppressed conditions. The pathogenesis of cryptococcosis reflects the interaction between host susceptibility, immune response to the infecting organism, and the virulence potential of the given C. neoformans strain. In North America, over 90 % of cases are caused by strains of serotype A, C. neoformans var. grubii, which are believed to be more pathogenic than strains of serotype D, C. neoformans var. neoformans (Mitchell & Perfect, 1995;Casadevall & Perfect, 1998).3These authors contributed equally to this work.

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Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line

Cited by 73 publications

References 30 publications

Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors

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Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line

Cited by 73 publications

References 30 publications

Requirement for CD4+T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Requirement for CD4+T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors

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Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice

Requirement for CD4⁺T Lymphocytes in Host Resistance againstCryptococcus neoformansin the Central Nervous System of Immunized Mice