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Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii

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ABSTRACT

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.

No MeSH data available.


Volcano plot showing degree of differential expression of mouse-derived genes in Charles River Laboratories mice compared to Taconic Biosciences. Log-transformed fold change in expression is plotted on the x-axis and log-transformed false discovery rate-adjusted p-values plotted on the y-axis. The red horizontal line represents the 0.1 p-value cutoff. Empty square: bsg (Basigin). Empty triangle: lgals9 (Galectin-9).
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Figure 6: Volcano plot showing degree of differential expression of mouse-derived genes in Charles River Laboratories mice compared to Taconic Biosciences. Log-transformed fold change in expression is plotted on the x-axis and log-transformed false discovery rate-adjusted p-values plotted on the y-axis. The red horizontal line represents the 0.1 p-value cutoff. Empty square: bsg (Basigin). Empty triangle: lgals9 (Galectin-9).

Mentions: Since sequencing also yielded mouse transcripts within the samples, differential gene expression amongst the murine transcripts was also analyzed. Fold change in gene expression and FDR adjusted p-values from the exact test are presented in the volcano plot in Figure 6. Twenty genes were differentially expressed with a p-value less than 0.1, 12 of which had p-values less than 0.05. Of these, 11 genes were significantly overrepresented in Charles River mice and one in Taconic mice. The overrepresented transcripts in Charles River mice include Galectin-9 (LGALS9), which is an important immune signaling molecule (Merani et al., 2015), and Basigin (bsg), a cell surface receptor whose expression is required for infection of RBCs by the human malaria parasite P. falciparum (Crosnier et al., 2011). All statistically significant mouse genes exhibited an effect size greater than 1.0, with the lowest being 1.16.


Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii
Volcano plot showing degree of differential expression of mouse-derived genes in Charles River Laboratories mice compared to Taconic Biosciences. Log-transformed fold change in expression is plotted on the x-axis and log-transformed false discovery rate-adjusted p-values plotted on the y-axis. The red horizontal line represents the 0.1 p-value cutoff. Empty square: bsg (Basigin). Empty triangle: lgals9 (Galectin-9).
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Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037233&req=5

Figure 6: Volcano plot showing degree of differential expression of mouse-derived genes in Charles River Laboratories mice compared to Taconic Biosciences. Log-transformed fold change in expression is plotted on the x-axis and log-transformed false discovery rate-adjusted p-values plotted on the y-axis. The red horizontal line represents the 0.1 p-value cutoff. Empty square: bsg (Basigin). Empty triangle: lgals9 (Galectin-9).
Mentions: Since sequencing also yielded mouse transcripts within the samples, differential gene expression amongst the murine transcripts was also analyzed. Fold change in gene expression and FDR adjusted p-values from the exact test are presented in the volcano plot in Figure 6. Twenty genes were differentially expressed with a p-value less than 0.1, 12 of which had p-values less than 0.05. Of these, 11 genes were significantly overrepresented in Charles River mice and one in Taconic mice. The overrepresented transcripts in Charles River mice include Galectin-9 (LGALS9), which is an important immune signaling molecule (Merani et al., 2015), and Basigin (bsg), a cell surface receptor whose expression is required for infection of RBCs by the human malaria parasite P. falciparum (Crosnier et al., 2011). All statistically significant mouse genes exhibited an effect size greater than 1.0, with the lowest being 1.16.

View Article: PubMed Central - PubMed

ABSTRACT

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.

No MeSH data available.