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Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

ABSTRACT: Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or sham control, and assayed host transcriptomic responses in peripheral blood. Infection with C. neoformans resulted in markedly greater fungal burden in the CNS than C. gattii, as well as slightly higher fungal burden in the lungs. A total of 389 genes were significantly differentially expressed in response to C. neoformans infection, which mainly clustered into pathways driving immune function, including complement activation and TH2-skewed immune responses. C. neoformans infection demonstrated dramatic up-regulation of complement-driven genes and greater up-regulation of alternatively activated macrophage activity than seen with C gattii. A 27-gene classifier was built, capable of distinguishing cryptococcal infection from animals with bacterial infection due to Staphylococcus aureus with 94% sensitivity and 89% specificity. Top genes from the murine classifiers were also differentially expressed in human PBMCs following infection, suggesting cross-species relevance of these findings. The host response, as manifested in transcriptional profiles, informs our understanding of the pathophysiology of cryptococcal infection and demonstrates promise for contributing to development of novel diagnostic approaches.

SUBMITTER: Holcomb ZE

PROVIDER: S-EPMC9143552 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

Holcomb Zachary E ZE Steinbrink Julie M JM Zaas Aimee K AK Betancourt Marisol M Tenor Jennifer L JL Toffaletti Dena L DL Alspaugh J Andrew JA Perfect John R JR McClain Micah T MT

Journal of fungi (Basel, Switzerland) 20220422 5

Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with Cryptococcus neoformans, Cryptococcus gattii, or sham control, and assayed host transcriptomic responses in peripheral blood. Infection with C. neoformans resulted in markedly greater fungal burden in the CNS than C. gattii, as well as slightly higher fungal burden ...[more]

PMID: 35628686

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Project description:BackgroundCryptococcosis is an opportunistic mycozoonosis of global significance in a wide variety of host species. In equines, cryptococcosis is uncommon, and sporadic cases have been reported with rhinitis, sinusitis, pneumonia, and meningitis. Cryptococcus spp. represents a potential risk for immunosuppressed and healthy persons. In Egypt, epidemiological data on cryptococcal infection in horses are limited. The current study was carried out to investigate the occurrence of Cryptococcus spp. in horses and its possible role in the epidemiology of such disease in Egypt. A total of 223 samples was collected from different localities in Egypt included 183 nasal swabs from horses, 28 nasal swabs from humans, and 12 soil samples. Bacteriological examination and the identification of Cryptococcus spp. were performed. Molecular serotyping of Cryptococcus spp. was determined by multiplex PCR using CNa-70S/A-CNb-49S/A. The virulence genes (LAC1, CAP59, and PLB1) of the identified isolates were detected by PCR. Moreover, sequencing and phylogenetic analysis of the C. gattii gene from horses, humans, and soil isolates found nearby were performed.ResultThe overall occurrence of Cryptococcus spp. in horses were 9.3, 25, and 10.7% in horses, the soil, and humans, respectively. Molecular serotyping of the Cryptococcus spp. isolates recovered from the nasal passages of horses proved that C. gattii (B), C. neoformans, and two hybrids between C. neoformans (A) and C. gattii (B) were identified. Meanwhile, in case of soil samples, the isolates were identified as C. gattii (B). The human isolates were serotyped as C. gattii in two isolates and C. neoformans in only one isolate. Molecular detection of some virulence genes (LAC1), (CAP59), and (PLB1) were identified in both C. gattii and C. neoformans isolates. The C. gattii gene amplicons of the isolates from horses, humans, and the soil were closely related.ConclusionThis study provides the first insights into the Egyptian horse ecology of Cryptococcus species and highlights the role of horses as asymptomatic carriers in disseminating the potentially pathogenic Cryptococcus spp. It also presents the possible risk of cryptococcosis infection in humans.

Dataset Information

Transcriptional Profiles Elucidate Differential Host Responses to Infection with Cryptococcus neoformans and Cryptococcus gattii.

Publications

Transcriptional Profiles Elucidate Differential Host Responses to Infection with <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>.

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