Airborne Cryptococcus neoformans: Particles from Pigeon Excreta Compatible with Alveolar Deposition

Powell, Kenneth E.; Dahl, Bernhoff A.; Weeks, Robert J.; Tosh, Fred E.

doi:10.1093/infdis/125.4.412

Cited by 82 publications

(26 citation statements)

References 7 publications

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“…These observations raise a possibility that capsular polysaccharides interfere with the BM-DC production of IL-12p40 in response to cryptococcal DNA, which may limit the significance of our findings. However, Cn is known to have no capsule or a thin capsule when infected via the airborne route, which may provide a benefit for them to reach the alveolar space (44). This notion suggests that DCs may encounter acapsular or thinly capsulated Cn and may be activated by DNA released from engulfed yeast cells under little influence of capsular polysaccharides at the early stage of infection.…”

Section: Discussionmentioning

confidence: 99%

Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway

Nakamura

Miyazato

Xiao

et al. 2008

The Journal of Immunology

100

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The mechanism of host cell recognition of Cryptococcus neoformans, an opportunistic fungal pathogen in immunocompromised patients, remains poorly understood. In the present study, we asked whether the DNA of this yeast activates mouse bone marrow-derived myeloid dendritic cells (BM-DCs). BM-DCs released IL-12p40 and expressed CD40 upon stimulation with cryptococcal DNA, and the response was abolished by treatment with DNase, but not with RNase. IL-12p40 production and CD40 expression were attenuated by chloroquine, bafilomycin A, and inhibitory oligodeoxynucleotides (ODN) that suppressed the responses caused by CpG-ODN. Activation of BM-DCs by cryptococcal DNA was almost completely abrogated in TLR9 gene-disrupted (TLR9−/−) mice and MyD88−/− mice, similar to that by CpG-ODN. In addition, upon stimulation with whole yeast cells of acapsular C. neoformans, TLR9−/− BM-DCs produced a lower amount of IL-12p40 than those from wild-type mice, and TLR9−/− mice were more susceptible to pulmonary infection with this fungal pathogen than wild-type mice, as shown by increased number of live colonies in lungs. Treatment of cryptococcal DNA with methylase resulted in reduced IL-12p40 synthesis by BM-DCs. Furthermore, using a luciferase reporter assay, cryptococcal DNA activated NF-κB in HEK293 cells transfected with the TLR9 gene. Finally, confocal microscopy showed colocalization of fluorescence-labeled cryptococcal DNA with CpG-ODN and the findings merged in part with the distribution of TLR9 in BM-DCs. Our results demonstrate that cryptococcal DNA causes activation of BM-DCs in a TLR9-dependent manner and suggest that the CpG motif-containing DNA may contribute to the development of inflammatory responses after infection with C. neoformans.

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Section: Discussionmentioning

confidence: 99%

Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway

Nakamura

Miyazato

Xiao

et al. 2008

The Journal of Immunology

100

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“…1955). A small percentage of C. neoformans from pigeon excreta has a diameter of less than 5-5 /im (Powell et al, 1972). C. neoformans was found to exist in soil in a relatively small, non-capsulated form with a diameter of less than 4-0/^m (Farhi, Bulmer & Tacker, 1970).…”

Section: Discussionmentioning

confidence: 99%

Hypersensitivity pneumonitis with antibodies to Cryptococcus neoformans

Miyagawa¹,

Ochi²,

Takahashi³

1978

Clin Experimental Allergy

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Summary Clinical and immunological studies were made in forty‐two patients diagnosed as suffering from hypersensitivity pneumonitis at Osaka Prefectural Habikino Hospital between 1973 and 1977. All the sera from forty‐one patients tested had high litres of antibody against Cryptococcus neoformans in indirect fluorescent antibody tests, and twelve also had precipitins against Cryptococcus neoformans polysaccharide. Only about 10% of control sera from patients with otherlung diseases had low titresof antibody against Cryptococcus neoformans. Antibody against Cryptococcus neoformans was also found frequently in the sera of asymptomatic members of the families of the patients. A possible relationship of Cryptococcus neoformans to hypersensitivity pneumonitis is suggested.

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“…Cryptococcosis in humans and animals is presumed to result from inhalation of infectious airborne organisms from the environment [2,12–14]. Fungal particles are deposited in the respiratory tract where they may be transient inhabitants or may colonize the mucosa [15,16]. Asymptomatic carriage of the nasal cavity of dogs and cats by C. neoformans var.…”

Section: Introductionmentioning

confidence: 99%

Asymptomatic carriage of Cryptococcus neoformans in the nasal cavity of the koala (Phascolarctos cinereus)

Connolly¹,

Krockenberger²,

Malík

et al. 2008

Med Mycol

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Over a 22‐month period, sequential nasal and skin swabs were obtained from 52 healthy captive koalas (Phascolarctos cinereus) from the Sydney region. Cryptococcus neoformans was isolated in 17 koalas from 64 of 262 (24%) nasal swabs and from nine of 262 (3%) skin swabs. Prevalence of nasal colonization varied seasonally from 12% (3/25) to 38% (10/26). Cryptococcus neoformans var. gattii alone was cultured from 37, var. neoformans alone from 22 and both varieties from five nasal swabs. Of 33 koalas sampled on three or more occasions, organisms were isolated persistently from six, occasionally from eight and never from 19. Two koalas were persistently and heavily (≥100 colonies/plate) colonized by C. neoformans var. gattii and two with var. neoformans. Isolation of C. neoformans var. gattii from the skin was low grade and sporadic. No koalas from which C. neoformans was persistently isolated showed clinical signs of cryptococcosis and all except one had a negative latex cryptococcal antigen test, therefore the nasal cavity was presumed to be colonized by, rather than infected with, C. neoformans. Preliminary observations of koalas from Coffs Harbour indicated a much higher prevalence of colonization by C. neoformans, suggesting that environmental factors influenced the extent of carriage by C. neoformans.

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Airborne Cryptococcus neoformans: Particles from Pigeon Excreta Compatible with Alveolar Deposition

Cited by 82 publications

References 7 publications

Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway

Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway

Hypersensitivity pneumonitis with antibodies to Cryptococcus neoformans

Asymptomatic carriage of Cryptococcus neoformans in the nasal cavity of the koala (Phascolarctos cinereus)

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