Dataset Information

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates.

ABSTRACT: Pathogens and hosts require rapid modulation of virulence and defense mechanisms at the infection axis, but monitoring such modulations is challenging. In studying the human fungal pathogen Cryptococcus neoformans, mouse and rabbit infection models are often employed to shed light on the disease mechanisms but that may not be clinically relevant. In this study, we developed an animal infection model using the non-human primate cynomolgus monkey Macaca fascicularis. In addition, we systematically profiled and compared transcriptional responses between the infected mice and the cynomolgus monkey, using simultaneous or dual RNA next-generation sequencing. We demonstrated that there are shared but distinct transcriptional profiles between the two models following C. neoformans infection. Specifically, genes involved in immune and inflammatory responses are all upregulated. Osteoclastogenesis and insulin signaling are also significantly co-regulated in both models and disrupting an osteoclastogenesis-associated gene (OC-STAMP) or the insulin-signaling process significantly altered the host tolerance to C. neoformans. Moreover, C. neoformans was shown to activate metal sequestration, dampen the sugar metabolism, and control cell morphology during infection. Taking together, we described the development of a non-human primate model of cryptococcosis that allowed us to perform an in-depth analysis and comparison of transcriptome profiles during infections of two animal models and conceptually identify host genes important in disease responses. This study provides new insights in understanding fungal pathogenesis mechanisms that potentially facilitate the identification of novel drug targets for the treatment of cryptococcal infection.

SUBMITTER: Li H

PROVIDER: S-EPMC6675133 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates.

Li Hailong H Li Yanjian Y Sun Tianshu T Du Wei W Li Chao C Suo Chenhao C Meng Yang Y Liang Qiaojing Q Lan Tian T Zhong Manli M Yang Sheng S Niu Cheng C Li Dancheng D Ding Chen C

PLoS neglected tropical diseases 20190722 7

Pathogens and hosts require rapid modulation of virulence and defense mechanisms at the infection axis, but monitoring such modulations is challenging. In studying the human fungal pathogen Cryptococcus neoformans, mouse and rabbit infection models are often employed to shed light on the disease mechanisms but that may not be clinically relevant. In this study, we developed an animal infection model using the non-human primate cynomolgus monkey Macaca fascicularis. In addition, we systematically ...[more]

PMID: 31329596

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Project description:The bacterial component of the gastrointestinal tract microbiome is comprised of hundreds of species, the majority of which live in symbiosis with the host. The bacterial microbiome is influenced by host diet and disease history, and host genetics may additionally play a role. To understand the degree to which host genetics shapes the gastrointestinal tract microbiome, we studied fecal microbiomes in 4 species of nonhuman primates (NHPs) held in separate facilities but fed the same base diet. These animals include Chlorocebus pygerythrus, Chlorocebus sabaeus, Macaca mulatta, and Macaca nemestrina. We also followed gastrointestinal tract microbiome composition in 20 Macaca mulatta (rhesus macaques [RMs]) as they transitioned from an outdoor to indoor environment and compared 6 Chlorocebus pygerythrus monkeys that made the outdoor to indoor transition to their 9 captive-born offspring. We found that genetics can influence microbiome composition, with animals of different genera (Chlorocebus versus Macaca) having significantly different gastrointestinal (GI) microbiomes despite controlled diets. Animals within the same genera have more similar microbiomes, although still significantly different, and animals within the same species have even more similar compositions that are not significantly different. Significant differences were also not observed between wild-born and captive-born Chlorocebus pygerythrus, while there were significant changes in RMs as they transitioned into captivity. Together, these results suggest that the effects of captivity have a larger impact on the microbiome than other factors we examined within a single NHP species, although host genetics does significantly influence microbiome composition between NHP genera and species. IMPORTANCE Our data point to the degree to which host genetics can influence GI microbiome composition and suggest, within primate species, that individual host genetics is unlikely to significantly alter the microbiome. These data are important for the development of therapeutics aimed at altering the microbiome within populations of genetically disparate members of primate species.

Dataset Information

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates.

Publications

Unveil the transcriptional landscape at the Cryptococcus-host axis in mice and nonhuman primates.

Similar Datasets

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