Cryptococcal Meningitis and Sarcoidosis

Ross, John J.; Katz, Jordan

doi:10.1080/0036554021000026969

Cited by 33 publications

(19 citation statements)

References 22 publications

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“…Cryptococcal meningitis represents the most frequent clinical manifestation of disseminated cryptococcosis (37,38). To study whether the prolonged survival of mice treated with anti-CD40 and IL-2 is correlated with decreased organ fungal burdens, mice were sacrificed 1 day after completion of the treatment schedule, and fungal burdens in the brain and kidney were assessed.…”

Section: Resultsmentioning

confidence: 99%

Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis

et al. 2006

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Cryptococcus neoformans is a ubiquitous fungus that can cause life-threatening infections during immunosuppressive states such as AIDS and after bone marrow transplantation. In this study we investigated the antifungal efficacy of an agonist antibody to CD40, an important costimulator of immune function, in combination with interleukin 2 (IL-2) in a murine model of disseminated cryptococcosis. Only the combination of anti-CD40 and IL-2 significantly prolonged the survival time of infected mice. This protection was correlated with decreased yeast burdens in the brain and kidney. Increased immune cell populations in the spleens, as well as increased serum gamma interferon (IFN-␥) and tumor necrosis factor alpha levels were observed in infected mice treated with anti-CD40 and IL-2. Further experiments with IFN-␥ knockout mice demonstrated that the protection induced by anti-CD40 and IL-2 treatment was dependent on IFN-␥. Depletion of CD4 ؉ T cells did not affect the increased serum IFN-␥ levels induced by anti-CD40 and IL-2 treatment and, importantly, did not affect the antifungal effect of combination therapy. These studies indicate that immunotherapy using anti-CD40 and IL-2 has therapeutic potential in augmenting host resistance to disseminated cryptococcosis and that IFN-␥ is essential for efficacy.Cryptococcus neoformans is an encapsulated yeast that can cause significant disease in immunocompromised hosts. Although the pulmonary tract is considered to be the major infection route, meningitis and meningoencephalitis caused by dissemination of C. neoformans to the brain are the most common manifestations and the main reason for high mortality of cryptococcosis. In murine models, C. neoformans infection through the intravenous route has been used widely to study the pathology as well as treatment of disseminated cryptococcosis (1,5,10,31,35).CD40 is a member of the tumor necrosis factor alpha (TNF-␣) receptor family and is expressed on numerous cell types, including B cells, dendritic cells, and monocytes. CD40 ligand (CD154) is expressed on activated T cells and NK cells (44). The interaction of CD40 and its ligand is important for optimal T-cell responses and for inducing inflammatory cytokine production by monocytes and dendritic cells (3). CD40 stimulation is also critical for dendritic cell differentiation and function (9, 44). CD40 signaling plays an important role in various pathogenic processes, such as chronic inflammation, autoimmune disorders, graft-versus-host disease, and resistance to tumors (4,16,36). Agonist antibodies to CD40 have been shown to facilitate antibody responses to T-independent antigens by bypassing the need for CD4-mediated "help" (14). We have shown that the immune-potentiating effects of anti-CD40 are further augmented by coadministration of interleukin-2 (IL-2) (36). The importance of the CD40/CD40L interaction in host immune defense has been demonstrated for infections such as Leishmania, mycobacteria, and human immunodeficiency virus (16,39,45). Deficiencies in either CD40 or ...

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Section: Resultsmentioning

confidence: 99%

Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis

et al. 2006

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“…Our patient did not have any clinical features to suggest any of these diagnoses and after workup, the diagnosis of sarcoidosis was confirmed. The sternoclavicular joint can be involved because of infectious arthritis in sarcoidosis as these patients are at an increased risk of opportunistic infections because of the use of immunosuppressive therapy (10,11). However, the presence of sternoclavicular arthritis at the onset followed by polyarticular involvement a few days later and no prior use of immunosuppressive therapy make septic arthritis unlikely in our patient.…”

Section: Discussionmentioning

confidence: 75%

Sternoclavicular joint arthritis as the initial presentation of sarcoidosis

et al. 2018

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“…Meningeal disease, cranial neuropathies and hypothalamic pituitary dysfunction are the classic signs of neurosarcoidosis [6]. Manifestations of meningitis like fever, vomiting, headache are more common with crytpococcal meningitis in sarcoidosis when compared to neurosarcoidosis alone [3]. India ink staining and cryptococcal latex agglutination test were twice negative.…”

Section: Casementioning

confidence: 99%

“…A majority of patients develop respiratory system involvement [1]. Neurological involvement in sarcoidosis occurs in 5-15% of patients [2,3].…”

Section: Introductionmentioning

confidence: 99%

SIADH as presenting feature in a male with coexisting sarcoidosis and systemic lupus

Govindaraj¹,

Viswanathan²,

Remalayam³

et al. 2013

Med-Science

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Cryptococcal Meningitis and Sarcoidosis

Cited by 33 publications

References 22 publications

Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis

Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis

Sternoclavicular joint arthritis as the initial presentation of sarcoidosis

SIADH as presenting feature in a male with coexisting sarcoidosis and systemic lupus

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