Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, United States.
Department of Biology, The Pennsylvania State University, University Park, United States.
Elife. 2022 Nov 8;11:e70347. doi: 10.7554/eLife.70347.
Co-infected hosts, individuals that carry more than one infectious agent at any one time, have been suggested to facilitate pathogen transmission, including the emergence of supershedding events. However, how the host immune response mediates the interactions between co-infecting pathogens and how these affect the dynamics of shedding remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal changes in the shedding of the respiratory bacterium in rabbits with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more , by direct contact with an agar petri dish, than rabbits with bacteria alone. Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. To explain this variation in shedding an infection-immune model was developed and fitted to rabbits of each group. Simulations suggested that differences in the magnitude and duration of shedding could be explained by the effect of the two helminths on the relative contribution of neutrophils and specific IgA and IgG to neutralization in the respiratory tract. However, the interactions between infection and immune response at the scale of analysis that we used could not capture the rapid variation in the intensity of shedding of every rabbit. We suggest that fast and local changes at the level of respiratory tissue probably played a more important role. This study indicates that co-infected hosts are important source of variation in shedding, and provides a quantitative explanation into the role of helminths to the dynamics of respiratory bacterial infections.
同时感染两种及以上病原体的宿主被认为能够促进病原体的传播，包括超级传播事件的发生。然而，宿主的免疫反应如何介导同时感染的病原体之间的相互作用，以及这些相互作用如何影响脱落动力学，在很大程度上仍不清楚。我们使用实验室实验和建模方法来研究单一或两种胃肠道寄生虫物种感染的兔子的呼吸道细菌脱落的时间变化。实验数据表明，与单独感染细菌的兔子相比，同时感染一种或两种寄生虫的兔子通过直接接触琼脂培养皿，显著增加了 的脱落。同时感染的宿主比没有寄生虫的宿主更频繁地产生更高强度的超级脱落事件。为了解释这种脱落的变化，我们开发了一种感染免疫模型，并将其拟合到每组兔子中。模拟结果表明，脱落幅度和持续时间的差异可以用两种寄生虫对呼吸道中性粒细胞和特异性 IgA 和 IgG 相对贡献的影响来解释，这种相对贡献对 的中和作用。然而，我们使用的分析规模上的感染和免疫反应之间的相互作用并不能捕捉到每只兔子脱落强度的快速变化。我们认为，呼吸道组织层面的快速和局部变化可能起着更重要的作用。本研究表明，同时感染的宿主是脱落变异的重要来源，并为寄生虫在呼吸道细菌感染动力学中的作用提供了定量解释。
