Pulmonary Cryptococcosis in Solid Organ Transplant Recipients: Clinical Relevance of Serum Cryptococcal Antigen

Singh, Nina; Alexander, Barbara D.; Lortholary, Olivier; Dromer, Françoise; Gupta, Krishan Lal; John, George T.; Busto, Ramon Del; Klintmalm, Göran B.; Somani, Jyoti; Lyon, G. Marshall; Pursell, Kenneth; Stosor, Valentina; Muñóz, Patricia; Limaye, Ajit P.; Kalil, André C.; Pruett, Timothy L.; Garcia-Diaz, Julia; Humar, Atul; Houston, Sally; House, Andrew A.; Wray, Dannah; Orloff, Susan L.; Dowdy, Lorraine A.; Fisher, Robert A.; Heitman, Joseph; Wagener, Marilyn M.; Husain, Shahid

doi:10.1086/524738

Cited by 153 publications

(102 citation statements)

References 39 publications

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“…The incidence of cryptococcosis increases throughout the course of HIV infection and correlates with the loss of a Th1 response in HIV-infected patients (1) and with a Th2-type cytokine profile in transplant recipients (48). Our data indicate that the loss of Th1 cytokines significantly reduces the ability of macrophages to deal with Cryptococcus and prevents efficient cryptococcal clearance in HIV-infected patients and, therefore, that proinflammatory cytokines may be a useful therapeutic agent for the treatment of cryptococcosis.…”

Section: Discussionmentioning

confidence: 75%

Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism byCryptococcus neoformans

2009

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The pathogenic yeast Cryptococcus neoformans and C. gattii commonly cause severe infections of the central nervous system in patients with impaired immunity but also increasingly in immunocompetent individuals. Cryptococcus is phagocytosed by macrophages but can then survive and proliferate within the phagosomes of these infected host cells. Moreover, Cryptococcus is able to escape into the extracellular environment via a recently discovered nonlytic mechanism (termed expulsion or extrusion). Although it is well established that the host's cytokine profile dramatically affects the outcome of cryptococcal disease, the molecular basis for this effect is unclear. Here, we report a systematic analysis of the influence of Th1, Th2, and Th17 cytokines on the outcome of the interaction between macrophages and cryptococci. We show that Th1 and Th17 cytokines activate, whereas Th2 cytokines inhibit, anticryptococcal functions. Intracellular yeast proliferation and cryptococcal expulsion rates were significantly lower after treatment with the Th1 cytokines gamma interferon and tumor necrosis factor alpha and the Th17 cytokine interleukin-17 (IL-17). Interestingly, however, the Th2 cytokines IL-4 and IL-13 significantly increased intracellular yeast proliferation while reducing the occurrence of pathogen expulsion. These results help explain the observed poor prognosis associated with the Th2 cytokine profile (e.g., in human immunodeficiency virus-infected patients).

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Section: Discussionmentioning

confidence: 75%

Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism byCryptococcus neoformans

2009

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“…A negative serum cryptococcal antigen in patients without HIV infection does not exclude cryptococcosis, and CSF antigen testing and fungal cultures should be performed in those with meningoencephalitis (50). Serum antigen has a lower diagnostic yield for isolated pulmonary cryptococcosis (51)(52)(53). In cases with focal disease such as cryptococcoma or pulmonary lesions, histopathologic evaluation of all available biopsy material should be performed.…”

Section: Donormentioning

confidence: 99%

Donor-Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice

Singh

Huprikar

Burdette

et al. 2012

American Journal of Transplantation

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160

161

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“…In contrast, Th2 cytokines, such as IL-4 and IL-13, reduce the host's ability to deal with C. neoformans in vivo (13,31,78,140). The incidence of cryptococcosis increases throughout the course of HIV infection and correlates with the loss of the Th1 response in HIV-infected patients (3) and with a Th2 cytokine profile in transplant patients (171). Thus, the Th1-Th2-Th17 balance is essential for the survival of cryptococci.…”

Section: Adaptive Immune Response To Cryptococcusmentioning

confidence: 99%

Cryptococcal Interactions with the Host Immune System

2010

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Opportunistic pathogens have become of increasing medical importance over the last decade due to the AIDS pandemic. Not only is cryptococcosis the fourth-most-common fatal infectious disease in sub-Saharan Africa, but also Cryptococcus is an emerging pathogen of immunocompetent individuals. The interaction between Cryptococcus and the host's immune system is a major determinant for the outcome of disease. Despite initial infection in early childhood with Cryptococcus neoformans and frequent exposure to C. neoformans within the environment, immunocompetent individuals are generally able to contain the fungus or maintain the yeast in a latent state. However, immune deficiencies lead to disseminating infections that are uniformly fatal without rapid clinical intervention. This review will discuss the innate and adaptive immune responses to Cryptococcus and cryptococcal strategies to evade the host's defense mechanisms. It will also address the importance of these strategies in pathogenesis and the potential of immunotherapy in cryptococcosis treatment.

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Pulmonary Cryptococcosis in Solid Organ Transplant Recipients: Clinical Relevance of Serum Cryptococcal Antigen

Abstract: A positive serum cryptococcal antigen test result in SOT recipients with pulmonary cryptococcosis appears to reflect extrapulmonary or more advanced radiographic disease.

Cited by 153 publications

References 39 publications

Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism byCryptococcus neoformans

Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism byCryptococcus neoformans

Donor-Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice

Cryptococcal Interactions with the Host Immune System

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