Pérez-Umphrey Anna A, Miller Jeremy, Tulman Edan R, Garrett-Larsen Jesse, Vinkler Michal, Langwig Kate, Geary Steven J, Adelman James S, Hawley Dana M
Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
Department of Biological Sciences, University of Memphis, Memphis, TN, USA.
bioRxiv. 2025 Aug 24:2025.08.20.671316. doi: 10.1101/2025.08.20.671316.
Variability in acquired protection, whether from prior pathogen exposure or vaccination, is increasingly recognized as a key determinant of host population-level variation in disease traits. It remains unclear whether this extends to the within-host physiological environment and what the consequences are for reinfecting pathogens. Here, we asked whether prior pathogen exposure of hosts induces gene expression heterogeneity in the host and/or pathogen during infection. We quantified gene expression following high-dose pathogen challenge of house finches () previously given controlled, varied exposure histories to a bacterial pathogen (; MG). To measure gene expression heterogeneity, we collected transcriptomic data from two host tissues (conjunctiva and spleen), and, simultaneously, from pathogen infecting the primary site of infection (conjunctiva). In the conjunctiva, but not the spleen, prior pathogen exposure induced significant heterogeneity in host gene expression relative to pathogen-naïve hosts. Further, hosts that received a lower prior exposure dose rather than a higher primary dose showed the greatest within-group heterogeneity in expression during re-challenge. Functional enrichment analyses for significantly variable host genes indicated an over-representation of terms involved in the immune system's response to pathogens, namely a diversified inflammatory response, in birds with prior pathogen exposure. The infecting pathogen from the conjunctiva followed similar patterns of heterogeneity in host gene expression, where pathogen infecting hosts with prior exposure had more heterogeneous expression than those infecting pathogen-naïve hosts. While the exact mechanisms that underlie greater variation in gene expression cannot be resolved by this study, our results are consistent with the hypothesis that prior host exposure induces a within-host environment that promotes heterogeneous gene expression across both hosts and pathogens. This suggests that to understand the coevolutionary dynamics of infectious diseases we must consider not only the genetic sequence variation, but also gene expression variation in host and pathogen.
获得性保护的变异性，无论是源于先前的病原体暴露还是疫苗接种，越来越被认为是宿主群体层面疾病特征变异的关键决定因素。目前尚不清楚这是否延伸到宿主内部的生理环境以及对再次感染病原体有何影响。在这里，我们研究了宿主先前的病原体暴露是否会在感染期间诱导宿主和/或病原体中的基因表达异质性。我们对家朱雀（Carpodacus mexicanus）进行了高剂量病原体攻击，这些家朱雀先前已被给予对一种细菌病原体（Mycoplasma gallisepticum；MG）的受控、不同暴露史，然后对基因表达进行了量化。为了测量基因表达异质性，我们从两个宿主组织（结膜和脾脏）以及同时从感染主要感染部位（结膜）的病原体中收集了转录组数据。在结膜而非脾脏中，相对于未接触过病原体的宿主，先前的病原体暴露诱导了宿主基因表达的显著异质性。此外，先前暴露剂量较低而非初次剂量较高的宿主在再次攻击期间表现出组内最大的表达异质性。对显著可变的宿主基因进行的功能富集分析表明，在先前接触过病原体的鸟类中，参与免疫系统对病原体反应的术语（即多样化的炎症反应）过度富集。来自结膜的感染病原体在宿主基因表达中遵循类似的异质性模式，即感染先前暴露宿主的病原体比感染未接触过病原体宿主的病原体具有更异质的表达。虽然本研究无法解析基因表达更大变异背后的确切机制，但我们的结果与以下假设一致：先前的宿主暴露会诱导宿主内部环境，促进宿主和病原体之间的异质基因表达。这表明，为了理解传染病的协同进化动态，我们不仅必须考虑遗传序列变异，还必须考虑宿主和病原体中的基因表达变异。
