Phagocytosis and growth inhibition of Cryptococcus neoformans by human alveolar macrophages

Reardon, Christine Campbell; Kim, Sue J.; Wagner, Randall P.; Koziel, Henry; Kornfeld, Hardy

doi:10.1097/00002030-199606000-00006

Cited by 29 publications

(13 citation statements)

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“…Because dendritic cells and alveolar macrophages play a critical role in the early innate protective host response against C. neoformans (71) and are associated with natural resistance to progressive infection (62), it is likely that functional defects of these cell populations also contributed to the increased susceptibility of the Tg mice to C. neoformans infection. Blood monocytes and alveolar macrophages from HIV-infected patients have impaired fungistatic activity against C. neoformans (72)(73)(74)(75)(76).…”

Section: Discussionmentioning

confidence: 99%

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

et al. 2013

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e Cryptococcus neoformans var. grubii is the most frequent cause of AIDS-associated cryptococcosis worldwide, while Cryptococcus gattii usually infects immunocompetent people. To understand the mechanisms which cause differential susceptibility to these cryptococcal species in HIV infection, we established and characterized a model of cryptococcosis in CD4C/HIV MutA transgenic (Tg) mice expressing gene products of HIV-1 and developing an AIDS-like disease. Tg mice infected intranasally with C. neoformans var. grubii strain H99 or C23 consistently displayed reduced survival compared to non-Tg mice at three graded inocula, while shortened survival of Tg mice infected with C. gattii strain R265 or R272 was restricted to a single high inoculum. HIV-1 transgene expression selectively augmented systemic dissemination to the liver and spleen for strains H99 and C23 but not strains R265 and R272. Histopathologic examination of lungs of Tg mice revealed large numbers of widely scattered H99 cells, with a minimal inflammatory cell response, while in the non-Tg mice H99 was almost completely embedded within extensive mixed inflammatory cell infiltrates. In contrast to H99, R265 was dispersed throughout the lung parenchyma and failed to induce a strong inflammatory response in both Tg and non-Tg mice. HIV-1 transgene expression reduced pulmonary production of CCL2 and CCL5 after infection with H99 or R265, and production of these two chemokines was lower after infection with R265. These results indicate that an altered immune response in these Tg mice markedly enhances C. neoformans but not C. gattii infection. This model therefore provides a powerful new tool to further investigate the immunopathogenesis of cryptococcosis.

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Section: Discussionmentioning

confidence: 99%

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

et al. 2013

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“…Activation of macrophages harboring cryptococci is a central effector mechanism in immunity to C. neoformans (30,64,65). Whereas in mice T cells and B cells only express IL-4R type 1 and therefore can only respond to IL-4, macrophages express IL-4R type 2, which can respond to IL-4 and also IL-13 (59).…”

Section: Discussionmentioning

confidence: 99%

IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans

Müller

Stenzel

Köhler

et al. 2007

The Journal of Immunology

247

275

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In the murine model of Cryptococcus neoformans infection Th1 (IL-12/IFN-γ) and Th17 (IL-23/IL-17) responses are associated with protection, whereas an IL-4-dependent Th2 response exacerbates disease. To investigate the role of the Th2 cytokine IL-13 during pulmonary infection with C. neoformans, IL-13-overexpressing transgenic (IL-13Tg+), IL-13-deficient (IL-13−/−), and wild-type (WT) mice were infected intranasally. Susceptibility to C. neoformans infection was found when IL-13 was induced in WT mice or overproduced in IL-13Tg+ mice. Infected IL-13Tg+ mice had a reduced survival time and higher pulmonary fungal load as compared with WT mice. In contrast, infected IL-13−/− mice were resistant and 89% of these mice survived the entire period of the experiment. Ag-specific production of IL-13 by susceptible WT and IL-13Tg+ mice was associated with a significant type 2 cytokine shift but only minor changes in IFN-γ production. Consistent with enhanced type 2 cytokine production, high levels of serum IgE and low ratios of serum IgG2a/IgG1 were detected in susceptible WT and IL-13Tg+ mice. Interestingly, expression of IL-13 by susceptible WT and IL-13Tg+ mice was associated with reduced IL-17 production. IL-13 was found to induce formation of alternatively activated macrophages expressing arginase-1, macrophage mannose receptor (CD206), and YM1. In addition, IL-13 production led to lung eosinophilia, goblet cell metaplasia and elevated mucus production, and enhanced airway hyperreactivity. This indicates that IL-13 contributes to fatal allergic inflammation during C. neoformans infection.

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“…This histological characteristic may be supported by a previous report indicating that bronchoalveolar lavage cells from early HIV-infected individuals did not have an intrinsic defect in fungistasis of cryptococci. 40 In addition to the lack of typical Langhans giant cells, the reactive histiocytes and multinucleated giant cells revealed that, while there was mostly normal phagocytic function, there was a decrease in the ability to kill cryptococci. The essential feature of the pulmonary lesions in patients with AIDS is the proliferation of cryptococci with reactive histiocytosis and a much lesser lymphocytic infiltration, which is, very possibly, the morphological response to cryptococcal infection in patients with manifest T-cell dysfunction.…”

Section: Granulomatous Response In Aids Patients With Variously Impaimentioning

confidence: 98%

Granuloma and cryptococcosis

Shibuya

Hirata

Omuta

et al. 2005

Journal of Infection and Chemotherapy

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Phagocytosis and growth inhibition of Cryptococcus neoformans by human alveolar macrophages

Cited by 29 publications

References 0 publications

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans

Granuloma and cryptococcosis

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