Comparison of spleen transcriptomes of two wild rodent species reveals differences in the immune response against Borrelia afzelii

Abstract

Different host species often differ considerably in susceptibility to a given pathogen, but the causes of such differences are rarely known. The natural hosts of the tick‐transmitted bacterium Borrelia afzelii, which is one of causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Previous studies have shown that B. afzelii‐infected bank voles (Myodes glareolus) have about ten times higher bacterial load than infected yellow‐necked mice (Apodemus flavicollis), indicating that these two species differ in resistance. In this study, we compared the immune response to B. afzelii infection in these host species by using RNA sequencing to quantify gene expression in spleen. Gene set enrichment analysis (GSEA) showed that several immune pathways were down‐regulated in infected animals in both bank voles and yellow‐necked mice. Moreover, IFNα response was up‐regulated in B. afzelii‐infected yellow‐necked mice, while IL6 signaling and the complement pathway were down‐regulated in infected bank voles; differences in regulation of these three pathways between bank voles and yellow‐necked mice could thus contribute to the difference in resistance to B. afzelii between the species. This study provides knowledge of gene expression induced by a zoonotic pathogen in its natural host, and possible species‐specific regulation of immune responses associated with resistance.

Comparative transcriptome analysis of Peromyscus leucopus and C3H mice infected with the Lyme disease pathogen

“…The present results are similar to the findings of a previous study, where the spleen transcriptome analyses of B. afzelii -infected and uninfected bank voles ( Myodes glareolus ) and yellow-necked mice ( Apodemus flavicollis ) were performed ( Zhong et al., 2020 ). Although both animal species are considered natural reservoir hosts of B. afzelii in Europe ( Zhong et al., 2019 ), Borreliella -infected bank voles have on average a magnitude higher spirochetal loads in their tissues ( Raberg, 2012 ; Zhong et al., 2019 ).…”

“…Although both animal species are considered natural reservoir hosts of B. afzelii in Europe ( Zhong et al., 2019 ), Borreliella -infected bank voles have on average a magnitude higher spirochetal loads in their tissues ( Raberg, 2012 ; Zhong et al., 2019 ). The comparative analyses between infected and uninfected animals within each species identified only 8 and 5 DEGs in B. afzelii -infected bank voles and yellow-necked mice, respectively ( Zhong et al., 2020 ). Furthermore, similar to the current data, other study had also shown no significant involvement of inflammation or innate immunity genes, when transcriptomes of skin and blood samples taken at 5 weeks postinfection were compared between Bb strain Sh-2-82-infected and uninfected P. leucopus mice ( Long et al., 2019 ).…”

Divergence in Coding Sequence and Expression of Different Functional Categories of Immune Genes between Two Wild Rodent Species

“…De novo transcriptome assemblies contained 842,299 and 761,841 contigs for bank vole and yellow-necked mouse, respectively. A series of filtering steps resulted in the retention of 13,631 contigs and 13,744 contigs in bank vole and yellow-necked mouse, respectively (see Zhong et al 2020 for more details regarding de novo transcriptome assemblies). The orthology between bank vole and yellow-necked mouse genes was determined by Reciprocal Best Hit (RBH) via BLASTp, which resulted in 10,931 one-to-one orthologs.…”

“…In previous analyses of gene expression in spleen of wild-caught naturally B. afzelii -infected and uninfected bank voles and yellow-necked mice, we found that the two species respond in partly different ways to B. afzelii infection. Specifically, B. afzelii infection is associated with up-regulation of IFNα-signaling in yellow-necked mice, but down-regulation of IL6 signaling and the complement system pathway in bank voles ( Zhong et al 2020 ). These differences in immune response presumably contribute to the observed difference in B. afzelii infection intensity between the two species ( Råberg 2012 ; Strandh and Råberg 2015 ).…”

“…These differences in immune response presumably contribute to the observed difference in B. afzelii infection intensity between the two species ( Råberg 2012 ; Strandh and Råberg 2015 ). In the present study, we use the dataset from Zhong et al (2020) , but instead of focusing on differences between the two species in the response to a specific pathogen, we analyze divergence in expression between species regardless of infections status.…”