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

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.


Related in: MedlinePlus

C57BL/6 mice from Taconic exhibit reduced parasitemia compared to mice from Charles River. Mice were infected with 105P. yoelii pRBCs. Percent parasitemia was determined on the indicated days. Data (mean ± SD) are cumulative results (n = 7–8 mice per group) from two independent experiments.
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Figure 1: C57BL/6 mice from Taconic exhibit reduced parasitemia compared to mice from Charles River. Mice were infected with 105P. yoelii pRBCs. Percent parasitemia was determined on the indicated days. Data (mean ± SD) are cumulative results (n = 7–8 mice per group) from two independent experiments.

Mentions: C57BL/6N mice from Taconic and Charles River were infected with P. yoelii pRBCs. Parasitemia in Taconic mice peaked 13 days post-infection at ∼15% and was cleared by 23 days post-infection (Figure 1). Charles River mice exhibited higher parasite burden, peaking at ∼60% parasitemia 19 days post-infection and delayed clearance (day 29 post-infection) compared to Taconic mice (Figure 1). These data are consistent with previous observations that showed P. yoelii infection of C57BL/6 mice from Taconic and Jackson Laboratories had lower parasitemia than C57BL/6 mice from Charles River, National Cancer Institute, and Envigo (formally Harlan; Villarino et al., 2016).


Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii
C57BL/6 mice from Taconic exhibit reduced parasitemia compared to mice from Charles River. Mice were infected with 105P. yoelii pRBCs. Percent parasitemia was determined on the indicated days. Data (mean ± SD) are cumulative results (n = 7–8 mice per group) from two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: C57BL/6 mice from Taconic exhibit reduced parasitemia compared to mice from Charles River. Mice were infected with 105P. yoelii pRBCs. Percent parasitemia was determined on the indicated days. Data (mean ± SD) are cumulative results (n = 7–8 mice per group) from two independent experiments.
Mentions: C57BL/6N mice from Taconic and Charles River were infected with P. yoelii pRBCs. Parasitemia in Taconic mice peaked 13 days post-infection at ∼15% and was cleared by 23 days post-infection (Figure 1). Charles River mice exhibited higher parasite burden, peaking at ∼60% parasitemia 19 days post-infection and delayed clearance (day 29 post-infection) compared to Taconic mice (Figure 1). These data are consistent with previous observations that showed P. yoelii infection of C57BL/6 mice from Taconic and Jackson Laboratories had lower parasitemia than C57BL/6 mice from Charles River, National Cancer Institute, and Envigo (formally Harlan; Villarino et al., 2016).

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.


Related in: MedlinePlus