Nowak Tristan A, Fernandes Carly, Malfetano Jill, Lasek-Nesselquist Erica, Combs Matthew, Strle Klemen, Burke Russell L, Lin Yi-Pin
Division of Infectious Diseases, Wadsworth Center, NYSDOH, Albany, NY, USA; Department of Biomedical Sciences, SUNY Albany, Albany, NY, USA.
Division of Infectious Diseases, Wadsworth Center, NYSDOH, Albany, NY, USA; Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.
Ticks Tick Borne Dis. 2024 Nov;15(6):102410. doi: 10.1016/j.ttbdis.2024.102410. Epub 2024 Nov 14.
Tolerance and resistance are two host eco-immunological strategies in response to microparasite invasion. In the strategy of "resistance", host responses are induced to decrease microparasite replication while the "tolerance" strategy allows hosts coexistence with microparasites by minimizing responses to avoid immune-mediated damage. The causative agent of Lyme disease is a group of genotypically diverse bacterial species, Borrelia burgdorferi sensu lato (Bb), which is transmitted by Ixodes ticks and persists in different reservoir animals. In North America, eastern fence lizards (Sceloporus undulatus) can be fed on by Ixodes ticks but are incompetent to one genotype of Bb (i.e., ospC type A). However, field-collected lizards showed evidence of previous infection by Bb strains with undefined genotypes. Supporting this evidence, we introduced three genotypically different Bb strains individually to eastern fence lizards and found a Bb genotype-dependent manner of infectivity. We compared liver transcriptomics and observed elevated immune responses triggered by a lizard-incompetent Bb strain (strain B31). We showed two lizard-competent strains with one having no immunomodulation (strain B379) but the other developing upregulated immune responses (strain 297). These results suggest that genetic variation in microparasites both induces different host strategies for dealing with infection and determines microparasite fitness in the hosts. These findings demonstrate that Bb and eastern fence lizards can serve as a model to investigate the mechanisms underlying eco-immunological strategies of tolerance vs. resistance during host-microparasite interaction.
耐受和抗性是宿主针对微寄生虫入侵的两种生态免疫策略。在“抗性”策略中，宿主会引发反应以减少微寄生虫的复制，而“耐受”策略则通过最小化反应来避免免疫介导的损伤，从而使宿主与微寄生虫共存。莱姆病的病原体是一组基因多样的细菌物种，即伯氏疏螺旋体（Borrelia burgdorferi sensu lato，Bb），它由硬蜱传播，并在不同的储存宿主动物中持续存在。在北美，东部围栏蜥蜴（Sceloporus undulatus）会被硬蜱叮咬，但对一种Bb基因型（即ospC A型）不敏感。然而，野外采集的蜥蜴显示出曾感染过基因型未明确的Bb菌株的证据。为支持这一证据，我们将三种基因不同的Bb菌株分别引入东部围栏蜥蜴，发现了一种依赖于Bb基因型的感染方式。我们比较了肝脏转录组学，观察到一种蜥蜴不敏感的Bb菌株（B31菌株）引发了增强的免疫反应。我们展示了两种蜥蜴敏感的菌株，其中一种没有免疫调节作用（B379菌株），而另一种则引发了上调的免疫反应（297菌株）。这些结果表明，微寄生虫的基因变异既会诱导宿主采取不同的应对感染策略，也会决定微寄生虫在宿主体内的适应性。这些发现表明，Bb和东部围栏蜥蜴可作为一个模型，用于研究宿主 - 微寄生虫相互作用期间耐受与抗性的生态免疫策略背后的机制。
