Incomplete immunity in a natural animal-microbiota interaction selects for higher pathogen virulence
Incomplete immunity in a natural animal-microbiota interaction selects for higher pathogen virulence
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DOI：
10.1016/j.cub.2024.02.015
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发表时间：
2024-03-25
期刊：
影响因子：
9.2
通讯作者：
King，Kayla C.
中科院分区：
文献类型：
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作者：
Hoang，Kim L.;Read，Timothy D.;King，Kayla C.
预计恢复的宿主中的不完全免疫在群体中重新感染时有利于更致命的病原体。1定植动物的微生物群可以产生类似的持久的部分免疫应答，允许感染但抑制疾病的严重性。2我们追踪了一种广泛传播的病原体的进化轨迹（铜绿假单胞菌），实验性地通过由天然微生物群成员（伯克利假单胞菌）免疫致敏的线虫群体传代。这种细菌可以诱导由有丝分裂原活化蛋白激酶（MAPK）信号通路调节的基因，该信号通路有效地赋予对病原体诱导的死亡的保护，尽管感染。幼稚的）或免疫受损的（敲除MAPK直系同源物的突变体）对照群体。尽管有较高的毒力，病原体分子进化的免疫引发的主机是缓慢的，受到限制。相比之下，在免疫受损宿主中进化的病原体的特征在于大量的基因组分化和减弱的毒力。这些发现直接归因于微生物群诱导的不完全宿主免疫是塑造新型传染病毒力和进化动力学的重要力量。
Incomplete immunity in recovered hosts is predicted to favor more virulent pathogens upon re-infection in the population.1The microbiota colonizing animals can generate a similarly long-lasting, partial immune response, allowing for infection but dampened disease severity.2We tracked the evolutionary trajectories of a widespread pathogen (Pseudomonas aeruginosa), experimentally passaged through populations of nematodes immune-primed by a natural microbiota member (P. berkeleyensis). This bacterium can induce genes regulated by a mitogen-activated protein kinase (MAPK) signaling pathway effective at conferring protection against pathogen-induced death despite infection.3Across host populations, this incomplete immunity selected for pathogens more than twice as likely to kill as those evolved in non-primed (i.e., naive) or immune-compromised (mutants with a knockout of the MAPK ortholog) control populations. Despite the higher virulence, pathogen molecular evolution in immune-primed hosts was slow and constrained. In comparison, evolving pathogens in immune-compromised hosts were characterized by substantial genomic differentiation and attenuated virulence. These findings directly attribute the incomplete host immunity induced from microbiota as a significant force shaping the virulence and evolutionary dynamics of novel infectious diseases.